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·Î¹öÆ® ¿ÍÀιö±×(Robert A. Weinberg), ÀÌÇÑ¿õ
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(The)biology of cancer
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- Á¦ÈÞ¸ô ÁÖ¹® ½Ã °í°´º¸»ó, ÀϺΠÀ̺¥Æ® Âü¿© ¹× ÁõÁ¤Ç° ÁõÁ¤, ÇÏ·ç/´çÀÏ ¹è¼Û¿¡¼ Á¦¿ÜµÇ¹Ç·Î Âü°í ¹Ù¶ø´Ï´Ù.
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¾ÏÀÇ ºÐÀÚ»Ó ¾Æ´Ï¶ó, ¼¼Æ÷ »ý¹°ÇÐÀû ±âº»À» °øºÎÇÏ°íÀÚ ÇÏ´Â ÇлýµéÀ» À§ÇÑ ¡º¾ÏÀÇ »ý¹°ÇС». ¹®ÀåÀ» ÃÖ´ëÇÑ Á¤È®ÇÏ°Ô ¼¼úÇÏ¿© ¾Ï »ý¹°ÇÐÀÇ ¿ø¸®¸¦ ¼³µæ·Â ÀÖ°Ô Á¤¸®ÇÏ¸é¼ Áß¿äÇÑ Á¤º¸¸¦ dzºÎÇÏ°Ô ´ã¾Æ³Â´Ù. ÁÖ¿ä ½ÇÇèÀ» ¼Ò°³ÇÏ¿© ¹ß°ßÀÇ ¹¦¹Ì¸¦ ÁÖ¸é¼ Çö´ëÀÇ ¾Ï »ý¹°ÇÐÀÇ °³³äÀû ±âº»ÀÌ µÇ´Â »ç½Ç¿¡ ´ëÇÑ ÅëÂû·ÂÀ» Á¦°øÇÑ´Ù. ¾Æ¿ï·¯ ±×¸²Àº ¸í·áÇÏ°Ô Ä÷¯·Î ½Ç¾î ÀÌÇظ¦ µµ¿ÍÁÖ°í ÀÖ´Ù.
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1Àå ¼¼Æ÷¿Í »ý¸íüÀÇ »ý¹°Çаú À¯ÀüÇÐ
1.1MendelÀº À¯ÀüÇÐÀÇ ±âº» ¹ýÄ¢µéÀ» È®¸³Çß´Ù 1.2 Mendelian genetics´Â Darwinian evolutionÀ» µÞ¹ÞħÇÑ´Ù 1.3 Mendelian genetics´Â gene°ú chromosome ¸ðµÎÀÇ ÇൿÀ» °áÁ¤ÇÑ´Ù 1.4 ChromosomeÀº ´ëºÎºÐÀÇ cancer cell¿¡¼ º¯ÇØ ÀÖ´Ù 1.5 Cancer¸¦ À¯¹ßÇÏ´Â mutationÀº germ line (»ý½Ä¼¼Æ÷)°ú soma (ü¼¼Æ÷) µÎ °÷ ÀüºÎ¿¡¼ ¹ß»ýÇÑ´Ù 1.6 DNA ¼Ó¿¡ ÀÖ´Â genotypeÀº proteinÀ» ÅëÇØ phenotypeÀ» ¸¸µç´Ù 1.7 Gene expression patternÀº phenotypeµµ Á¶ÀýÇÑ´Ù 1.8 Transcription factor´Â gene expressionÀ» Á¶ÀýÇÑ´Ù 1.9 Metazoa (Èı¸µ¿¹°)´Â ¿À·£ ÁøÈ ±â°£ µ¿¾È ±¸¼º ¼ººÐµéÀÌ º¸Á¸µÇ¾î Çü¼ºµÇ¾ú´Ù 1.10 Gene cloning ±â¼úÀº normal cell°ú malignant cellÀÇ ¿¬±¸¿¡ ´ëº¯ÇõÀ» °¡Á®¿Ô´Ù
2Àå CancerÀÇ º»Áú 2.1 Tumor´Â Á¤»ó¼¼Æ÷·ÎºÎÅÍ ¹ß»ýÇÑ´Ù 2.2 Tumor´Â ´Ù¾çÇÑ À¯ÇüÀÇ ºÐȼ¼Æ÷·ÎºÎÅÍ ¹ß»ýÇÑ´Ù 2.3 ¸î¸î À¯ÇüÀÇ Tumor´Â ÁÖ¿ä ºÐ·ù¹ýÀ» Àû¿ëÇϱâ ÀûÇÕÄ¡ ¾Ê´Ù 2.4 Cancer´Â Á¡ÁøÀûÀ¸·Î Çü¼ºµÈ´Ù 2.5 Tumor´Â Monoclonal GrowthÀÌ´Ù 2.6 Tumor´Â ¼·Î ´Ù¸¥ Áý´Ü¿¡¼ ¸Å¿ì ´Ù¸¥ ºóµµ·Î ¹ß»ýÇÑ´Ù 2.7 CancerÀÇ À§ÇèÀº »ýÈ°¾ç...½ÄÀ» Æ÷ÇÔÇÑ Æ¯Á¤ ÀÎÀÚ¿¡ ÀÇÇØ Áõ°¡ÇÒ ¼ö ÀÖ´Ù 2.8 Chemical (ÈÇй°Áú)Àº cancer¸¦ À¯¹ßÇÒ ¼ö ÀÖ´Ù 2.9 ¹°¸®Àû ¹× ÈÇÐÀû Carcinogen (¹ß¾Ï¹°Áú) ¸ðµÎ Mutagen (µ¹¿¬º¯ÀÌ¿ø)À¸·Î ÀÛ¿ëÇÑ´Ù 2.10 MutagenÀº ÀϺÎÀÇ Human Cancer¸¦ À¯¹ßÇÒ ¼ö ÀÖ´Ù 2.11 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
3Àå Tumor Virus 3.1 Peyton RousÀÇ chicken sarcoma (À°Á¾) virus ¹ß°ß 3.2 Rous sarcoma virus´Â infected cellÀ» transformation ½ÃŲ´Ù 3.3 TransformationÀÌ À¯ÁöµÇ±â À§Çؼ´Â RSV°¡ Áö¼ÓÀûÀ¸·Î ÇÊ¿äÇÏ´Ù 3.4 DNA ºÐÀÚ¸¦ °¡Áö°í ÀÖ´Â virus´Â cancer¸¦ ÀÏÀ¸Å³ ¼ö ÀÖ´Ù 3.5 Tumor virus´Â tumorigenecityÀÇ È¹µæ°ú °°Àº cell phenoytpe change¸¦ ÀÏÀ¸Å²´Ù 3.6 Tumor virus genomeÀº transform µÈ host cell DNAÀÇ ÀϺΰ¡ µÇ¾î Á¸¼ÓÇÑ´Ù 3.7 Retroviral genomeÀº °¨¿°µÈ ¼¼Æ÷ÀÇ chromosome¿¡ »ðÀԵȴ٠3.8 RSV¿¡ ÀÖ´Â src geneÀÇ ¶Ç ´Ù¸¥ ÇüÅ´ °¨¿°µÇÁö ¾ÊÀº ¼¼Æ÷ ³»¿¡µµ Á¸ÀçÇÑ´Ù 3.9 RSV´Â °¡Á®¿Â cellular geneÀ» ÀÌ¿ëÇÏ¿© cellÀ» transform ½ÃŲ´Ù 3.10 ôÃßµ¿¹°ÀÇ genomeÀº ¸¹Àº Á¾·ùÀÇ proto-oncogeneÀ» °¡Áö°í ÀÖ´Ù 3.11 ´À¸®°Ô transformation ÇÏ´Â retrovirusµéÀº ±×µéÀÇ genomeÀ» cellular gene ¿·¿¡ ³¢¿ö ³ÖÀ½À¸·Î½á proto-oncogeneÀ» È°¼ºÈÇÑ´Ù 3.12 ¾î¶² retrovirusµéÀº Å»ýÀûÀ¸·Î oncogeneÀ» °¡Áö°í ÀÖ´Ù 3.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
4Àå Cellular Oncogene 4.1 Endogenous retrovirusÀÇ È°¼ºÈ¿¡ ÀÇÇØ Á¾¾çÀº ÃËÁøµÉ ¼ö Àִ°¡? 4.2 DNA transfectionÀº nonviral oncogeneÀ» ã´Â Àü·«À» Á¦°øÇÑ´Ù 4.3 Àΰ£ tumor ¼¼Æ÷ÁÖ¿¡¼ ¹ß°ßµÈ oncogeneÀº transforming retrovirus¿¡ ÀÇÇØ ¿î¹ÝµÇ´Â °Í°ú ¾î¶°ÇÑ ¿¬°ü¼ºÀÌ ÀÖÀ»±î? 4.4 Proto-oncogeneÀº ´Ü¹éÁúÀÇ ¹ßÇöÀ̳ª ±¸Á¶¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â À¯ÀüÀû º¯È¿¡ ÀÇÇØ È°¼ºÈµÉ ¼ö ÀÖ´Ù 4.5 Myc ÁÖÁ¦¿¡ ´ëÇÑ º¯ÁÖ°î : Myc oncogeneÀº Àû¾îµµ 3 °³ÀÇ ºÎ°¡ÀûÀÎ µ¶Æ¯ÇÑ ¸ÞÄ¿´ÏÁòÀ» ÅëÇØ »ý±æ ¼ö ÀÖ´Ù 4.6 proteinÀÇ ´Ù¾çÇÑ ±¸Á¶Àû º¯È´Â oncogene È°¼ºÈ·Î À̾îÁú ¼ö ÀÖ´Ù 4.7 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
5Àå Growth Factor¿Í Receptor, ±×¸®°í Cancer 5.1 Á¤»óÀûÀÎ metazoan cell (ÈÄ»ýµ¿¹°¼¼Æ÷)µéÀº ¼·ÎÀÇ »ý¸íÇö»óÀ» Á¶ÀýÇÑ´Ù 5.2 Tyrosine kinase·Î¼ÀÇ Src ´Ü¹éÁúÀÇ ±â´É 5.3 EGF receptor´Â tyrosine kinase·Î ÀÛ¿ëÇÑ´Ù 5.4 º¯ÇüµÈ growth factor receptor´Â oncoprotein (Á¾¾ç´Ü¹éÁú)À¸·Î ±â´É ÇÒ ¼ö ÀÖ´Ù 5.5 Growth factor À¯ÀüÀÚ´Â oncogeneÀÌ µÉ ¼ö ÀÖ´Ù : sisÀÇ »ç·Ê 5.6 Transphosphorylation (ÀλêÀüÀÌÀÛ¿ë)Àº recepto1Àå ¼¼Æ÷¿Í »ý¸íüÀÇ »ý¹°Çаú À¯ÀüÇÐ
1.1 MendelÀº À¯ÀüÇÐÀÇ ±âº» ¹ýÄ¢µéÀ» È®¸³Çß´Ù 2
1.2 Mendelian genetics´Â Darwinian evolutionÀ» µÞ¹ÞħÇÑ´Ù 4
1.3 Mendelian genetics´Â gene°ú chromosome ¸ðµÎÀÇ ÇൿÀ» °áÁ¤ÇÑ´Ù 7
1.4 ChromosomeÀº ´ëºÎºÐÀÇ cancer cell¿¡¼ º¯ÇØ ÀÖ´Ù 10
1.5 Cancer¸¦ À¯¹ßÇÏ´Â mutationÀº germ line (»ý½Ä¼¼Æ÷)°ú soma (ü¼¼Æ÷) µÎ °÷ ÀüºÎ¿¡¼ ¹ß»ýÇÑ´Ù 11
1.6 DNA ¼Ó¿¡ ÀÖ´Â genotypeÀº proteinÀ» ÅëÇØ phenotypeÀ» ¸¸µç´Ù 15
1.7 Gene expression patternÀº phenotypeµµ Á¶ÀýÇÑ´Ù 19
1.8 Transcription factor´Â gene expressionÀ» Á¶ÀýÇÑ´Ù 21
1.9 Metazoa (Èı¸µ¿¹°)´Â ¿À·£ ÁøÈ ±â°£ µ¿¾È ±¸¼º ¼ººÐµéÀÌ º¸Á¸µÇ¾î Çü¼ºµÇ¾ú´Ù 22
1.10 Gene cloning ±â¼úÀº normal cell°ú malignant cellÀÇ ¿¬±¸¿¡ ´ëº¯ÇõÀ» °¡Á®¿Ô´Ù 23
2Àå CancerÀÇ º»Áú
2.1 Tumor´Â Á¤»ó¼¼Æ÷·ÎºÎÅÍ ¹ß»ýÇÑ´Ù 26
2.2 Tumor´Â ´Ù¾çÇÑ À¯ÇüÀÇ ºÐȼ¼Æ÷·ÎºÎÅÍ ¹ß»ýÇÑ´Ù 28
2.3 ¸î¸î À¯ÇüÀÇ Tumor´Â ÁÖ¿ä ºÐ·ù¹ýÀ» Àû¿ëÇϱâ ÀûÇÕÄ¡ ¾Ê´Ù 34
2.4 Cancer´Â Á¡ÁøÀûÀ¸·Î Çü¼ºµÈ´Ù 34
2.5 Tumor´Â Monoclonal GrowthÀÌ´Ù 39
2.6 Tumor´Â ¼·Î ´Ù¸¥ Áý´Ü¿¡¼ ¸Å¿ì ´Ù¸¥ ºóµµ·Î ¹ß»ýÇÑ´Ù 43
2.7 CancerÀÇ À§ÇèÀº »ýÈ°¾ç½ÄÀ» Æ÷ÇÔÇÑ Æ¯Á¤ ÀÎÀÚ¿¡ ÀÇÇØ Áõ°¡ÇÒ ¼ö ÀÖ´Ù 45
2.8 Chemical (ÈÇй°Áú)Àº cancer¸¦ À¯¹ßÇÒ ¼ö ÀÖ´Ù 46
2.9 ¹°¸®Àû ¹× ÈÇÐÀû Carcinogen (¹ß¾Ï¹°Áú) ¸ðµÎ Mutagen (µ¹¿¬º¯ÀÌ¿ø)À¸·Î ÀÛ¿ëÇÑ´Ù 48
2.10 MutagenÀº ÀϺÎÀÇ Human Cancer¸¦ À¯¹ßÇÒ ¼ö ÀÖ´Ù 52
2.11 °³¿ä ¹× Àü¸Á 54
Key concept 55
Thought question 56
Additional reading 56
3Àå Tumor Virus
3.1 Peyton RousÀÇ chicken sarcoma (À°Á¾) virus ¹ß°ß 58
3.2 Rous sarcoma virus´Â infected cellÀ» transformation ½ÃŲ´Ù 61
3.3 TransformationÀÌ À¯ÁöµÇ±â À§Çؼ´Â RSV°¡ Áö¼ÓÀûÀ¸·Î ÇÊ¿äÇÏ´Ù 63
3.4 DNA ºÐÀÚ¸¦ °¡Áö°í ÀÖ´Â virus´Â cancer¸¦ ÀÏÀ¸Å³ ¼ö ÀÖ´Ù 65
3.5 Tumor virus´Â tumorigenecityÀÇ È¹µæ°ú °°Àº cell phenoytpe change¸¦ ÀÏÀ¸Å²´Ù 69
3.6 Tumor virus genomeÀº transform µÈ host cell DNAÀÇ ÀϺΰ¡ µÇ¾î Á¸¼ÓÇÑ´Ù 71
3.7 Retroviral genomeÀº °¨¿°µÈ ¼¼Æ÷ÀÇ chromosome¿¡ »ðÀԵȴ٠73
3.8 RSV¿¡ ÀÖ´Â src geneÀÇ ¶Ç ´Ù¸¥ ÇüÅ´ °¨¿°µÇÁö ¾ÊÀº ¼¼Æ÷ ³»¿¡µµ Á¸ÀçÇÑ´Ù 75
3.9 RSV´Â °¡Á®¿Â cellular geneÀ» ÀÌ¿ëÇÏ¿© cellÀ» transform ½ÃŲ´Ù 77
3.10 ôÃßµ¿¹°ÀÇ genomeÀº ¸¹Àº Á¾·ùÀÇ proto-oncogeneÀ» °¡Áö°í ÀÖ´Ù 80
3.11 ´À¸®°Ô transformation ÇÏ´Â retrovirusµéÀº ±×µéÀÇ genomeÀ» cellular gene ¿·¿¡ ³¢¿ö ³ÖÀ½À¸·Î½á proto-oncogeneÀ» È°¼ºÈÇÑ´Ù 82
3.12 ¾î¶² retrovirusµéÀº Å»ýÀûÀ¸·Î oncogeneÀ» °¡Áö°í ÀÖ´Ù 84
3.13 °³¿ä ¹× Àü¸Á 86
Key concept 88
Thought question 90
Additional reading 90
4Àå Cellular Oncogene
4.1 Endogenous r tyrosine kinase ÀÛ¿ëÀÇ ±âÃÊ°¡ µÈ´Ù 5.7 Æ÷À¯·ù ¼¼Æ÷´Â ¿©·¯ °¡Áö ÇüÅÂÀÇ receptor¸¦ ÅëÇØ ÁÖº¯ ȯ°æ°ú ¼ÒÅëÇÒ ¼ö ÀÖ´Ù 5.8 Integrin receptor´Â ¼¼Æ÷¿Í extracellular matrixÀÇ °áÇÕÀ» ÀÎÁöÇÑ´Ù 5.9 Downstream signaling cascadeÀÇ ¿ä¼ÒÀÎ Ras proteinÀº G proteinÀ¸·Î¼ ÀÛ¿ëÇÑ´Ù 5.10 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
6Àå ¼¼Æ÷ÁúÀÇ ½ÅÈ£Àü´Þ ȸ·Î´Â CancerÀÇ ´Ù¾çÇÑ Æ¯Â¡À» ÇÁ·Î±×·¥ÇÑ´Ù 6.1 ¼¼Æ÷ Ç¥¸é¿¡¼ ÇÙÀ¸·Î Àü´ÞµÇ´Â ½ÅÈ£ °æ·Î 6.2 Ras proteinÀº º¹ÀâÇÑ signaling cascadeÀÇ Á߽ɿ¡ ÀÖ´Ù 6.3 Tyrosine phosphorylationÀº À§Ä¡ Á¦¾î¸¦ ÅëÇÏ¿© ¸¹Àº cytoplasmic signaling proteinµéÀÇ È°µ¿À» Á¦¾îÇÑ´Ù 6.4 Growth factor receptor°¡ Ras¸¦ È°¼ºÈÇÏ°í, signaling specificity¸¦ ȹµæÇÏ´Â µ¥¿¡´Â SH2 groupÀÌ Áß¿äÇÑ ¿ªÇÒÀ» ¼öÇàÇÑ´Ù 6.5 Ras·Î ºÎÅÍ ½ÃÀ۵Ǵ 3°³ÀÇ ÁÖ¿ä downstream signaling pathway¿¡ kinase cascade°¡ Æ÷ÇԵȴ٠6.6 RasÀÇ µÎ ¹ø° downstream pathway´Â inositol lipid¿Í Akt/PKB kinase¸¦ Á¶ÀýÇÑ´Ù 6.7 ¼¼ ¹ø° Ras Á¶Àý °æ·Î´Â RasÀÇ ¸Õ ģôÀÎ, RalÀ» ÅëÇÏ¿© ÀÛ¿ëÇÑ´Ù 6.8 Jak-STAT pathway´Â plasma membrane¿¡¼ ÇÙÀ¸·Î ½ÅÈ£¸¦ Àü´ÞÇÑ´Ù 6.9 Cell adhesion receptor¿¡¼ ¹æÃâµÈ signalÀº growth factor receptor·ÎºÎÅÍÀÇ signal°ú ÇÕÃÄÁø´Ù 6.10 Wnt?¥â-catenin pathway°¡ cell proliferation¿¡ ±â¿©ÇÑ´Ù 6.11 G-protein-coupled receptor´Â Á¤»óÀûÀÎ proliferation°ú neplastic proliferation ¸ðµÎ¸¦ À¯µµÇÒ ¼ö ÀÖ´Ù 6.12 ³× °³ÀÇ signaling pathway°¡ Á¤»ó°ú Á¾¾ç proliferation¿¡ ¿©·¯ ¹æ¹ýÀ¸·Î ±â¿©ÇÑ´Ù 6.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
7Àå Tumor Suppressor Gene 7.1 Cell fusion experiment (¼¼Æ÷À¶ÇÕ ½ÇÇè)´Â ¾ÏÀÇ ÇüÁúÀÌrecessive (¿¼º)ÀÓÀ» º¸¿©ÁØ´Ù 7.2 Cancer cell phenotypeÀÇ ¿¼ºÀû Ư¡À» ¾Ë±â À§ÇÏ¿© À¯ÀüÇÐÀû ÀÌÇØ°¡ ÇÊ¿äÇÏ´Ù 7.3 Retinoblastoma tumor¿¡¼ ¾ò¾îÁø tumor suppressor geneÀÇ À¯ÀüÀû ³Á¦¿¡ ´ëÇÑ Çعý 7.4 Ãʱâ tumor cell¿¡¼ Á¤»ó tumor suppressor geneÀÌ Á¦°ÅµÇ´Â ¹æ¹ý 7.5 Tumor¿¡¼ Rb geneÀÇ LOH´Â ÈçÈ÷ ÀϾ´Â Çö»óÀÌ´Ù 7.6 Loss of Heterozygosity¸¦ ÅëÇØ tumor suppressor geneÀ» ãÀ» ¼ö ÀÖ´Ù 7.7 °¡Á··ÂÀÌ ÀÖ´Â ¾ÏÀº mutant tumor suppressor geneÀÇ À¯Àü¿¡ ÀÇÇØ ³ªÅ¸³´Ù 7.8 PromoterÀÇ methylationµµ tumor suppressor geneÀ» ºÒÈ°¼ºÈ½ÃÅ°´Â Áß¿äÇÑ ±âÀüÀÌ´Ù 7.9 Tumor suppressor gene°ú proteinÀÇ ´Ù¾çÇÑ ÀÛ¿ë °æ·Î 7.10 NF1 protein, Ras signalingÀÇ negative regulator 7.11 Apc´Â ´ëÀåÀÇ crypt¿¡¼ cellÀÇ À̵¿À» ÃËÁøÇÑ´Ù 7.12 Von Hippel-Lindau disease: pVHL´Â hypoxic response (Àú»ê¼Ò ¹ÝÀÀ)¸¦ Á¶ÀýÇÑ´Ù 7.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
8Àå pRb¿Í Cell Cycle ClockÀÇ Á¶Àý 8.1 Extracellular signal¿¡ ÀÇÇÑ cell cycle Á¶Àý 8.2 G1ÀÇ Æ¯Á¤ÇÑ phase¿¡ °áÁ¤µÇ´Â cell growth¿Í quiescence 8.3 Cell cycle °áÁ¤¿¡¼ ÇÙ½ÉÀû ¿ªÇÒÀ» ÇÏ´Â cyclin°ú cyclin-dependent kinase 8.4 Cyclin?CDK complex¿Í À̵éÀÇ ¾ïÁ¦Á¦ 8.5 Virus oncogeneÀ» ÅëÇÑ RbÀÇ cell cycle Á¶Àý ±âÀü 8.6 pRb¿Í restriction-point gate 8.7 Transcription factor E2F´Â pRb·Î ÇÏ¿©±Ý growth-versus-quiescenceÀÇ °áÁ¤À» Á¶ÀýÇÏ°Ô ÇÑ´Ù 8.8 Mitogen°ú pRbÀÇ phosphorylation 8.9 Myc¿¡ ÀÇÇÑ Rb phosphorylationÀÇ Á¶Àý°ú cell cycle progression Á¶ÀýÀÇ ÀÌ»ó 8.10 TGF-¥â´Â cell cycleÀ» ¾ïÁ¦ÇÏ°í pRbÀÇ phosphorylationÀ» ¸·´Â´Ù 8.11 pRbÀÇ ±â´É°ú differentiationÀÇ Á¶ÀýÀº ¸Å¿ì ¹ÐÁ¢ÇÏ°Ô ¿¬°üµÇ¾î ÀÖ´Ù 8.12 ´ëºÎºÐÀÇ cancer¿¡¼ pRb ±â´ÉÀÌ Á¤»óÀûÀ¸·Î Á¶ÀýµÇÁö ¸øÇÑ´Ù 8.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
9Àå p53°ú Apoptosis: Master Guardian ¹× Executioner 9.1 Papovavirus¿¡ ÀÇÇÑ p53 ¹ß°ß 9.2 Tumor suppressor geneÀ¸·Î¼ p53ÀÇ ¹ß°ß 9.3 Mutant p53¿¡ ÀÇÇÑ wild type p53ÀÇ ±â´É ¾ïÁ¦ 9.4 ªÀº lifetimeÀ» °¡Áö´Â p53 9.5 p53 Áõ°¡¸¦ ÀÏÀ¸Å°´Â signal (½ÅÈ£µé) 9.6 DNA damage¿Í growth signalÀÇ Á¶Àý ÀÌ»óÀ¸·Î ÀÎÇÑ p53ÀÇ ¾ÈÁ¤È 9.7 p53ÀÇ ¿î¸íÀ» °áÁ¤ÇÏ´Â Mdm2¿Í ARF 9.8 ARF¿Í p53¿¡ ÀÇÇÑ apoptosis´Â intracellular signalingÀ» °¨½ÃÇÏ¿© cancerÀÇ ¹ß»ýÀ» ¾ïÁ¦ÇÑ´Ù 9.9 DNA ¼Õ»ó¿¡ ¹ÝÀÀÇÏ¿© p53Àº transcription factor·Î ±â´ÉÇÏ¿© cell cycle ÁøÇàÀ» ¸·°í repair°úÁ¤À» µ½´Â´Ù 9.10 p53¿¡ ÀÇÇÑ apoptotic death program 9.11 p53ÀÇ inactivationÀº tumor progressionÀÇ ¸¹Àº ´Ü°è¿¡¼ incipient (ÃʱâÀÇ) cancer cell¿¡ ÀÌÁ¡À» Á¦°øÇÑ´Ù 9.12 Inherited p53 mutation°ú cancerÀÇ ¹ß»ý 9.13 Apoptosis´Â ¸Å¿ì º¹ÀâÇÑ ±âÀüÀ̸ç Á¾Á¾ mitochondria¿¡ ÀÇÁ¸ÇÑ´Ù 9.14 Apoptosis¸¦ À¯¹ßÇÏ´Â µÎ °¡Áö ¹æ¹ý 9.15 Cancer cellµéÀº apoptosis machineryÀÇ ÀϺΠȤÀº Àüü¸¦ inactivation ½ÃÅ°±â À§ÇÏ¿© ¼ö¸¹Àº ¹æ¹ýÀ» âÁ¶Çس½´Ù 9.16 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
10Àå ¿µ¿øÇÑ »ý¸í: Cell Immortalization°ú Tumorigenesis 10.1 Normal cellÀÇ growth divisionÀº Á¤ÇØÁø Ƚ¼ö¸¸Å ÀÌ·ç¾îÁø´Ù 10.2 Cancer cellÀÇ immortalization 10.3 CellÀÇ physiological stress¿¡ ÀÇÇÑ replication ¾ïÁ¦ 10.4 Cultured cellÀÇ proliferationÀº ÀÚ½ÅÀÇ chromosome ³»¿¡ Á¸ÀçÇÏ´Â telomere¿¡ ÀÇÇØ Á¦Çѵȴ٠10.5 Telomere´Â ½±°Ô replication µÇÁö ¾Ê´Â º¹ÀâÇÑ ºÐÀÚ ±¸Á¶ÀÌ´Ù 10.6 Cancer cellÀº telomerase ¹ßÇöÀ» ÅëÇÏ¿© crisis¸¦ ȸÇÇÇÑ´Ù 10.7 human cancer cellÀÇ Áõ½Ä¿¡ ÀÖ¾î¼ Áß¿äÇÑ telomeraseÀÇ ¿ªÇÒ 10.8 ÀϺΠimmortalized cellÀº telomerase ¾øÀ̵µ telomere¸¦ À¯ÁöÇÑ´Ù 10.9 Telomere´Â human cell°ú mouse cell¿¡¼ ¼·Î ´Ù¸¥ ±â´ÉÀ» ÇÑ´Ù 10.10 Telomerase negative mouse¿¡¼ tumor¿¡ ´ëÇÑ susceptibility (°¨¼ö¼º) 10.11 Telomerase negative mouse¿¡ ³ªÅ¸³ª´Â Çö»ó°ú ½ÇÁ¦ human cancer¿¡¼ ³ªÅ¸³ª´Â cancer ¹ß»ý ±âÀü 10.12 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
11Àå Multi-Step Tumorigenesis 11.1 ´ëºÎºÐÀÇ human cancer´Â ¼ö½Ê ³â¿¡ °ÉÃļ ¹ß´ÞÇÑ´Ù 11.2 Histopathology (Á¶Á÷º´¸®ÇÐ)´Â multi-step tumor formationÀÇ Áõ°Å¸¦ Á¦½ÃÇÑ´Ù 11.3 Colonic growth¿¡ µû¸¥ À¯ÀüÀû º¯È¿Í tumor progression 11.4 Multi-step tumor progression°ú familial polyposis ¹× field cancerization 11.5 TumorÀÇ ¹ß»ýÀº DarwinÀÇ ¹ýÄ¢À» µû¸£´Â °Íó·³ º¸Àδ٠11.6 Tumor stem cell (Á¾¾çÁٱ⼼Æ÷)°ú tumor progression ±×¸®°í DarwinÀÇ ¸ðµ¨ 11.7 Clonal successionÀÇ liner path´Â ¾ÏÀ» Áö³ªÄ¡°Ô ´Ü¼øȽÃŲ´Ù 11.8 Darwin model¿¡ ´ëÇÑ ½ÇÇèÀû Áõ¸íÀÇ ³Á¡ 11.9 Single mutated gene (´ÜÀÏ À¯ÀüÀû º¯ÀÌ)Àº normal cellÀ» transformation ½ÃÅ°Áö ¸øÇÑ´Ù 11.10 TransformationÀº Àû¾îµµ 2?3 °³ÀÇ À¯ÀüÀû º¯ÀÌ°¡ ÇÊ¿äÇÏ´Ù 11.11 Transgenic mouse¸¦ ÀÌ¿ëÇÑ oncogeneÀÇ »óÈ£ÀÛ¿ë ¹× multi-step cell transformation ¿¬±¸ 11.12 Human cellÀº immortalization°ú transformation¿¡ °ÇÑ ÀúÇ×¼ºÀÌ ÀÖ´Ù 11.13 Nonmutagenic carcinogen (¼¼Æ÷ ¼ºÀå ÃËÁø ¹°Áú µî)¿¡ ÀÇÇÑ tumorigenesis 11.14 Tumor promoter·Î¼ÀÇ µ¶¼º ¹°Áú°ú ¼ºÀå ÃËÁø ¹°Áú (toxic and mitogenic agent) 11.15 Human°ú ½ÇÇè¿ë mouse¿¡¼ tumor promoter·Î¼ÀÇ chronic inflammation (¸¸¼º ¿°Áõ) 11.16 Inflammation °ü·Ã tumor promotionÀÇ signaling pathway 11.17 Tumor promoterÀº tumor progressionÀÇ ¼Óµµ¸¦ Á¶ÀýÇÏ´Â Áß¿äÇÑ °áÁ¤ ÀÎÀÚÀÌ´Ù 11.18 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
12Àå Genomic IntegrityÀÇ À¯Áö¿Í CancerÀÇ ¹ß»ý 12.1 retrovirusÀÇ È°¼ºÈ¿¡ ÀÇÇØ Á¾¾çÀº ÃËÁøµÉ ¼ö Àִ°¡? 92
4.2 DNA transfectionÀº nonviral oncogeneÀ» ã´Â Àü·«À» Á¦°øÇÑ´Ù 93
4.3 Àΰ£ tumor ¼¼Æ÷ÁÖ¿¡¼ ¹ß°ßµÈ oncogeneÀº transforming retrovirus¿¡ ÀÇÇØ ¿î¹ÝµÇ´Â °Í°ú ¾î¶°ÇÑ ¿¬°ü¼ºÀÌ ÀÖÀ»±î? 98
4.4 Proto-oncogeneÀº ´Ü¹éÁúÀÇ ¹ßÇöÀ̳ª ±¸Á¶¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â À¯ÀüÀû º¯È¿¡ ÀÇÇØ È°¼ºÈµÉ ¼ö ÀÖ´Ù 103
4.5 Myc ÁÖÁ¦¿¡ ´ëÇÑ º¯ÁÖ°î : Myc oncogeneÀº Àû¾îµµ 3 °³ÀÇ ºÎ°¡ÀûÀÎ µ¶Æ¯ÇÑ ¸ÞÄ¿´ÏÁòÀ» ÅëÇØ »ý±æ ¼ö ÀÖ´Ù 107
4.6 proteinÀÇ ´Ù¾çÇÑ ±¸Á¶Àû º¯È´Â oncogene È°¼ºÈ·Î À̾îÁú ¼ö ÀÖ´Ù 111
4.7 °³¿ä ¹× Àü¸Á 112
Key concept 115
Thought question 117
Additional reading 117
5Àå Growth Factor¿Í Receptor, ±×¸®°í Cancer
5.1 Á¤»óÀûÀÎ metazoan cell (ÈÄ»ýµ¿¹°¼¼Æ÷)µéÀº ¼·ÎÀÇ »ý¸íÇö»óÀ» Á¶ÀýÇÑ´Ù 121
5.2 Tyrosine kinase·Î¼ÀÇ Src ´Ü¹éÁúÀÇ ±â´É 123
5.3 EGF receptor´Â tyrosine kinase·Î ÀÛ¿ëÇÑ´Ù 126
5.4 º¯ÇüµÈ growth factor receptor´Â oncoprotein (Á¾¾ç´Ü¹éÁú)À¸·Î ±â´É ÇÒ ¼ö ÀÖ´Ù 129
5.5 Growth factor À¯ÀüÀÚ´Â oncogeneÀÌ µÉ ¼ö ÀÖ´Ù : sisÀÇ »ç·Ê 132
5.6 Transphosphorylation (ÀλêÀüÀÌÀÛ¿ë)Àº receptor tyrosine kinase ÀÛ¿ëÀÇ ±âÃÊ°¡ µÈ´Ù 135
5.7 Æ÷À¯·ù ¼¼Æ÷´Â ¿©·¯ °¡Áö ÇüÅÂÀÇ receptor¸¦ ÅëÇØ ÁÖº¯ ȯ°æ°ú ¼ÒÅëÇÒ ¼ö ÀÖ´Ù 141
5.8 Integrin receptor´Â ¼¼Æ÷¿Í extracellular matrixÀÇ °áÇÕÀ» ÀÎÁöÇÑ´Ù 147
5.9 Downstream signaling cascadeÀÇ ¿ä¼ÒÀÎ Ras proteinÀº G proteinÀ¸·Î¼ ÀÛ¿ëÇÑ´Ù 150
5.10 °³¿ä ¹× Àü¸Á 153
Key concept 157
Thought question 158
Additional reading 158
6Àå ¼¼Æ÷ÁúÀÇ ½ÅÈ£Àü´Þ ȸ·Î´Â CancerÀÇ ´Ù¾çÇÑ Æ¯Â¡À» ÇÁ·Î±×·¥ÇÑ´Ù
6.1 ¼¼Æ÷ Ç¥¸é¿¡¼ ÇÙÀ¸·Î Àü´ÞµÇ´Â ½ÅÈ£ °æ·Î 161
6.2 Ras proteinÀº º¹ÀâÇÑ signaling cascadeÀÇ Á߽ɿ¡ ÀÖ´Ù 164
6.3 Tyrosine phosphorylationÀº À§Ä¡ Á¦¾î¸¦ ÅëÇÏ¿© ¸¹Àº cytoplasmic signaling proteinµéÀÇ È°µ¿À» Á¦¾îÇÑ´Ù 166
6.4 Growth factor receptor°¡ Ras¸¦ È°¼ºÈÇÏ°í, signaling specificity¸¦ ȹµæÇÏ´Â µ¥¿¡´Â SH2 groupÀÌ Áß¿äÇÑ ¿ªÇÒÀ» ¼öÇàÇÑ´Ù 171
6.5 Ras·Î ºÎÅÍ ½ÃÀ۵Ǵ 3°³ÀÇ ÁÖ¿ä downstream signaling pathway¿¡ kinase cascade°¡ Æ÷ÇԵȴ٠173
6.6 RasÀÇ µÎ ¹ø° downstream pathway´Â inositol lipid¿Í Akt/PKB kinase¸¦ Á¶ÀýÇÑ´Ù 176
6.7 ¼¼ ¹ø° Ras Á¶Àý °æ·Î´Â RasÀÇ ¸Õ ģôÀÎ, RalÀ» ÅëÇÏ¿© ÀÛ¿ëÇÑ´Ù 183
6.8 Jak-STAT pathway´Â plasma membrane¿¡¼ ÇÙÀ¸·Î ½ÅÈ£¸¦ Àü´ÞÇÑ´Ù 185
6.9 Cell adhesion receptor¿¡¼ ¹æÃâµÈ signalÀº growth factor receptor·ÎºÎÅÍÀÇ signal°ú ÇÕÃÄÁø´Ù 186
6.10 Wnt?¥â-catenin pathway°¡ cell proliferation¿¡ ±â¿©ÇÑ´Ù 189
6.11 G-protein-coupled receptor´Â Á¤»óÀûÀÎ proliferation°ú neplastic proliferation ¸ðµÎ¸¦ À¯µµÇÒ ¼ö ÀÖ´Ù 191Tissue´Â mutationÀÇ ÃàÀûÀÌ Àß ÀϾÁö ¾Êµµ·Ï ±¸¼ºµÇ¾î ÀÖ´Ù 12.2 Stem cellÀº cancer¸¦ À¯µµÇÏ´Â mutagenesisÀÇ targetÀ¸·Î º¸Àδ٠12.3 Apoptosis¿Í drug pump, ±×¸®°í DNA replicationÀÇ mechanismÀº mutant stem cellÀÌ tissue¿¡ ÃàÀûµÇ´Â °ÍÀ» ¾ïÁ¦ÇÑ´Ù 12.4 ¼¼Æ÷ÀÇ genomeÀº DNA replication °úÁ¤¿¡¼ ¹ß»ýÇÏ´Â ¿À·ù·ÎºÎÅÍ À§ÇùÀ» ¹Þ´Â´Ù 12.5 ¼¼Æ÷ÀÇ genomeÀº endogenous biochemical process·ÎºÎÅÍ ²÷ÀÓ¾øÀÌ °ø°ÝÀ» ¹Þ´Â´Ù 12.6 ¼¼Æ÷ÀÇ genomeÀº ¶§¶§·Î exogenous mutagen°ú ±×µéÀÇ metabolite·ÎºÎÅÍ °ø°ÝÀ» ¹Þ´Â´Ù 12.7 ¼¼Æ÷´Â mutagenÀÇ °ø°ÝÀ¸·ÎºÎÅÍ DNA¸¦ º¸È£Çϱâ À§ÇØ ´Ù¾çÇÑ ¹æ¾î ±âÀÛÀ» »ç¿ëÇÑ´Ù 12.8 Repair enzymeÀº mutagen¿¡ ÀÇÇØ º¯ÇüµÈ DNA¸¦ °íÄ£´Ù 12.9 Nucleotide excision repair¿Í base excision repair ±×¸®°í mismatch repairÀÇ ±âÀü¿¡ ¹ß»ýÇÑ inherited defect´Â specific cancer susceptibility syndromeÀ» À¯¹ßÇÑ´Ù 12.10 ´Ù¾çÇÑ Á¾·ùÀÇ DNA repair ±âÀÛ¿¡ »ý±ä defect´Â ¾ÆÁ÷ ¹àÇôÁöÁö ¾ÊÀº ±âÀÛÀ» ÅëÇØ cancer susceptibility¸¦ Áõ°¡½ÃŲ´Ù 12.11 Cancer cellÀÇ karyotypeÀº chromosome ±¸Á¶ÀÇ º¯Çü¿¡ ÀÇÇØ ÀÚÁÖ ¹Ù²ï´Ù 12.12 Cancer cellÀÇ karyotypeÀº chromosome ¼öÀÇ º¯Çü¿¡ ÀÇÇØ ÀÚÁÖ ¹Ù²ï´Ù 12.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional reading
13Àå Dialogue (´ëÈ)´Â Monologue (µ¶¹é)¸¦ ´ëüÇÑ´Ù : Heterotypic Interaction°ú AngiogenesisÀÇ »ý¹°ÇÐ 13.1 Á¤»ó »óÇÇ Á¶Á÷°ú Á¾¾ç »óÇÇ Á¶Á÷Àº ¼·Î ÀÇÁ¸ÇÏ´Â ¼¼Æ÷ À¯ÇüÀ¸·ÎºÎÅÍ Çü¼ºµÈ´Ù 13.2 Cancer cell lineÀ» Çü¼ºÇÏ´Â ¼¼Æ÷´Â heterotypic interaction ¾øÀÌ ¹ß´ÞÇÏ°í human tumor ³»¿¡ ÀÖ´Â ¼¼Æ÷ÀÇ Çൿ¿¡¼ ¹þ¾î³´Ù 13.3 Tumor´Â Ä¡·áµÇÁö ¾ÊÀº »óóÁ¶Á÷°ú °øÅëÁ¡ÀÌ ÀÖ´Ù 13.4 Stromal cellÀº tumorigenesisÀÇ active contributorÀÌ´Ù 13.5 Macrophage´Â È°¼ºÈµÈ tumor-associated stroma¿¡¼ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 13.6 Endothelial cell°ú À̵éÀÌ ¸¸µå´Â vesselÀº tumor·Î ÇÏ¿©±Ý circulation¿¡ ½±°Ô µé¾î°¥ ¼ö ÀÖ°Ô ÇÑ´Ù 13.7 Angiogenic switchÀÇ ¹Îø¼ºÀº Á¾¾ç Áõ½Ä¿¡ ÇʼöÀûÀÌ´Ù 13.8 Angiogenic switch´Â ³ôÀº º¹ÇÕü °úÁ¤À» ½ÃÀÛÇÏ°Ô ÇÑ´Ù 13.9 Ç÷°ü½Å»ýÀº »ý¸®Àû ÀúÇع°¿¡ ÀÇÇØ ¾ïÁ¦µÈ´Ù 13.10 ¾î¶² anti-angiogenesis therapyµéÀº cancerÀÇ Ä¡·á¿¡ ´ëÇÑ Àü¸ÁÀ» ¹à°Ô ÇØÁØ´Ù 13.11 °³¿ä¿Í Àü¸Á Key concept Thought question Additional reading
14Àå Cancer CellÀÇ À̵¿ : Invasion (ħÅõ)°ú Metastasis (ÀüÀÌ) 14.1 Cancer cellÀÌ primary tumor·ÎºÎÅÍ metastasis°¡ °¡´ÉÇÑ Àå¼Ò·Î À̵¿Çϱâ À§Çؼ´Â º¹ÀâÇÑ »ý¹°ÇÐÀû °úÁ¤À» °ÅÃÄ¾ß ÇÑ´Ù 14.2 Colonization (±ºÁýÀ» ÀÌ·ç´Â °Í)Àº invasion-metastasis cascade¿¡¼ °¡Àå º¹ÀâÇÏ°í ¾î·Á¿î ´Ü°èÀÌ´Ù 14.3 Epithelial-mesenchymal transition°ú ÀÌ¿Í °ü·ÃµÈ E-cadherinÀÇ ¹ßÇöÀÌ ¼Ò½ÇµÇ¸é carcinoma cellÀº invasiveÇÏ°Ô µÈ´Ù 14.4 Epithelial-mesenchymal transitionÀº stromal signal¿¡ ÀÇÇØ À¯µµµÇ±âµµ ÇÑ´Ù 14.5 EMT´Â embryogenesisÀÇ ÁÖ¿ä ´Ü°è¸¦ Á¶ÀýÇÏ´Â transcription factorµé¿¡ ÀÇÇÏ¿© program µÈ´Ù 14.6 Extracellular proteaseµéÀÌ invasiveness¿¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 14.7 Small Ras-like GTPase´Â adhesion°ú ¼¼Æ÷ÀÇ ¸ð¾ç, ±×¸®°í ¼¼Æ÷ÀÇ motility (¿îµ¿¼º)¸¦ Á¶ÀýÇÑ´Ù 14.8 ÀüÀÌÇÏ´Â ¼¼Æ÷´Â lymphatic vesselÀ» ÀÌ¿ëÇÏ¿© primary tumor·ÎºÎÅÍ ÆÛÁ® ³ª°£´Ù 14.9 ÆÛÁ® ³ª°£ cancer cellÀÌ ¾î¶² ±â°ü¿¡¼ ÀüÀ̸¦ Çü¼ºÇÒÁö¸¦ °áÁ¤ÇÏ´Â µ¥¿¡´Â ¸¹Àº ¿ä¼Ò°¡ °ü¿©ÇÑ´Ù 14.10 »À·Î ÀüÀ̵ǷÁ¸é osteoblast (Á¶°ñ¼¼Æ÷(ðãÍéá¬øà))¿Í osteoclast (ÆÄ°ñ(÷òÍé)¼¼Æ÷)ÀÇ subversionÀÌ ÇÊ¿äÇÏ´Ù 14.11 Metastasis suppressor gene (ÀüÀ̾ïÁ¦ À¯ÀüÀÚ)µéÀº metastatic phenotype (ÀüÀÌ Ç¥ÇöÇü)À» Á¶ÀýÇÑ´Ù 14.12 Occult (À°¾ÈÀ¸·Î º¸ÀÌÁö ¾Ê´Â) micrometastasis°¡ ¾Ï ȯÀÚÀÇ Àå±â »ýÁ¸À» À§ÇùÇÑ´Ù 14.13 °³¿ä ¹× Àü¸Á Key concept Thought question Additional r
6.12 ³× °³ÀÇ signaling pathway°¡ Á¤»ó°ú Á¾¾ç proliferation¿¡ ¿©·¯ ¹æ¹ýÀ¸·Î ±â¿©ÇÑ´Ù 193
6.13 °³¿ä ¹× Àü¸Á 197
Key concept 204
Thought question 207
Additional reading 207
7Àå Tumor Suppressor Gene
7.1 Cell fusion experiment (¼¼Æ÷À¶ÇÕ ½ÇÇè)´Â ¾ÏÀÇ ÇüÁúÀÌrecessive (¿¼º)ÀÓÀ» º¸¿©ÁØ´Ù 210
7.2 Cancer cell phenotypeÀÇ ¿¼ºÀû Ư¡À» ¾Ë±â À§ÇÏ¿© À¯ÀüÇÐÀû ÀÌÇØ°¡ ÇÊ¿äÇÏ´Ù 213
7.3 Retinoblastoma tumor¿¡¼ ¾ò¾îÁø tumor suppressor geneÀÇ À¯ÀüÀû ³Á¦¿¡ ´ëÇÑ Çعý 214
7.4 Ãʱâ tumor cell¿¡¼ Á¤»ó tumor suppressor geneÀÌ Á¦°ÅµÇ´Â ¹æ¹ý 216
7.5 Tumor¿¡¼ Rb geneÀÇ LOH´Â ÈçÈ÷ ÀϾ´Â Çö»óÀÌ´Ù 219
7.6 Loss of Heterozygosity¸¦ ÅëÇØ tumor suppressor geneÀ» ãÀ» ¼ö ÀÖ´Ù 221
7.7 °¡Á··ÂÀÌ ÀÖ´Â ¾ÏÀº mutant tumor suppressor geneÀÇ À¯Àü¿¡ ÀÇÇØ ³ªÅ¸³´Ù 224
7.8 PromoterÀÇ methylationµµ tumor suppressor geneÀ» ºÒÈ°¼ºÈ½ÃÅ°´Â Áß¿äÇÑ ±âÀüÀÌ´Ù 226
7.9 Tumor suppressor gene°ú proteinÀÇ ´Ù¾çÇÑ ÀÛ¿ë °æ·Î 232
7.10 NF1 protein, Ras signalingÀÇ negative regulator 233
7.11 Apc´Â ´ëÀåÀÇ crypt¿¡¼ cellÀÇ À̵¿À» ÃËÁøÇÑ´Ù 235
7.12 Von Hippel-Lindau disease: pVHL´Â hypoxic response (Àú»ê¼Ò ¹ÝÀÀ)¸¦ Á¶ÀýÇÑ´Ù 241
7.13 °³¿ä ¹× Àü¸Á 247
Key concept 252
Thought question 253
Additional reading 253
8Àå pRb¿Í Cell Cycle ClockÀÇ Á¶Àý
8.1 Extracellular signal¿¡ ÀÇÇÑ cell cycle Á¶Àý 256
8.2 G1ÀÇ Æ¯Á¤ÇÑ phase¿¡ °áÁ¤µÇ´Â cell growth¿Í quiescence 261
8.3 Cell cycle °áÁ¤¿¡¼ ÇÙ½ÉÀû ¿ªÇÒÀ» ÇÏ´Â cyclin°ú cyclin-dependent kinase 262
8.4 Cyclin?CDK complex¿Í À̵éÀÇ ¾ïÁ¦Á¦ 268
8.5 Virus oncogeneÀ» ÅëÇÑ RbÀÇ cell cycle Á¶Àý ±âÀü 273
8.6 pRb¿Í restriction-point gate 277
8.7 Transcription factor E2F´Â pRb·Î ÇÏ¿©±Ý growth-versus-quiescenceÀÇ °áÁ¤À» Á¶ÀýÇÏ°Ô ÇÑ´Ù 278
8.8 Mitogen°ú pRbÀÇ phosphorylation 282
8.9 Myc¿¡ ÀÇÇÑ Rb phosphorylationÀÇ Á¶Àý°ú cell cycle progression Á¶ÀýÀÇ ÀÌ»ó 284
8.10 TGF-¥â´Â cell cycleÀ» ¾ïÁ¦ÇÏ°í pRbÀÇ phosphorylationÀ» ¸·´Â´Ù 288
8.11 pRbÀÇ ±â´É°ú differentiationÀÇ Á¶ÀýÀº ¸Å¿ì ¹ÐÁ¢ÇÏ°Ô ¿¬°üµÇ¾î ÀÖ´Ù 292
8.12 ´ëºÎºÐÀÇ cancer¿¡¼ pRb ±â´ÉÀÌ Á¤»óÀûÀ¸·Î Á¶ÀýµÇÁö ¸øÇÑ´Ù 296
8.13 °³¿ä ¹× Àü¸Á 300
Key concept 304
Thought question 305
Additional reading 305
9Àå p53°ú Apoptosis: Master Guardian ¹× Executioner
9.1 Papovavirus¿¡ ÀÇÇÑ p53 ¹ß°ß 308
9.2 Tumor suppressor geneÀ¸·Î¼ p53ÀÇ ¹ß°ß 310
9.3 Mutant p53¿¡ ÀÇÇÑ wild type p53ÀÇ ±â´É ¾ïÁ¦ 311
9.4 ªÀº lifetimeÀ» °¡Áö´Â p53 314
9.5 p53 Áõ°¡¸¦ ÀÏÀ¸Å°´Â signal (½ÅÈ£µé) 315
9.6 DNA damage¿Í growth signalÀÇ Á¶Àý ÀÌ»óÀ¸·Î ÀÎÇÑ p53ÀÇ ¾ÈÁ¤È 317
9.7 p53ÀÇ ¿î¸íÀ» °áÁ¤ÇÏ´Â Mdm2¿Í ARF 318
9.8 ARF¿Í p53¿¡ ÀÇÇÑ apoptosis´Â intracellular signalingÀ» °¨½ÃÇÏ¿© cancerÀÇ ¹ß»ýÀ» ¾ïÁ¦ÇÑ´Ù 323
9.9 DNA ¼Õ»ó¿¡ ¹ÝÀÀÇÏ¿© p53Àº transcription factor·Î ±â´ÉÇÏ¿© cell cycle ÁøÇàÀ» ¸·°í repair°úÁ¤À» µ½´Â´Ù 325
9.10 p53¿¡ ÀÇÇÑ apoptotic death program 329
9.11 p53ÀÇ inactivationÀº tumor progressionÀÇ ¸¹Àº ´Ü°è¿¡¼ incipient (ÃʱâÀÇ) cancer cell¿¡ ÀÌÁ¡À» Á¦°øÇÑ´Ù 331
9.12 Inherited p53 mutation°ú cancerÀÇ ¹ß»ý 332
9.13 Apoptosis´Â ¸Å¿ì º¹ÀâÇÑ ±âÀüÀ̸ç Á¾Á¾ mitochondria¿¡ ÀÇÁ¸ÇÑ´Ù 334
9.14 Apoptosis¸¦ À¯¹ßÇÏ´Â µÎ °¡Áö ¹æ¹ý 342
9.15 Cancer cellµéÀº apoptosis machineryÀÇ ÀϺΠȤÀº Àüü¸¦ inactivation ½ÃÅ°±â À§ÇÏ¿© ¼ö¸¹Àº ¹æ¹ýÀ» âÁ¶Çس½´Ù 346
9.16 °³¿ä ¹× Àü¸Á 350
Key concept 354
Thought question 355
Additional reading 355
10Àå ¿µ¿øÇÑ »ý¸í: Cell Immortalization°ú Tumorigenesis
10.1 Normal cellÀÇ growth divisionÀº Á¤ÇØÁø Ƚ¼ö¸¸Å ÀÌ·ç¾îÁø´Ù 358
10.2 Cancer cellÀÇ immortalization 361
10.3 CellÀÇ physiological stress¿¡ ÀÇÇÑ replication ¾ïÁ¦ 365
10.4 Cultured cellÀÇ proliferationÀº ÀÚ½ÅÀÇ chromosome ³»¿¡ Á¸ÀçÇÏ´Â telomere¿¡ ÀÇÇØ Á¦Çѵȴ٠368
10.5 Telomere´Â ½±°Ô replication µÇÁö ¾Ê´Â º¹ÀâÇÑ ºÐÀÚ ±¸Á¶ÀÌ´Ù 373
10.6 Cancer cellÀº telomerase ¹ßÇöÀ» ÅëÇÏ¿© crisis¸¦ ȸÇÇÇÑ´Ù 376
10.7 human cancer cellÀÇ Áõ½Ä¿¡ ÀÖ¾î¼ Áß¿äÇÑ telomeraseÀÇ ¿ªÇÒ 381
10.8 ÀϺΠimmortalized cellÀº telomerase ¾øÀ̵µ telomere¸¦ À¯ÁöÇÑ´Ù 383
10.9 Telomere´Â human cell°ú mouse cell¿¡¼ ¼·Î ´Ù¸¥ ±â´ÉÀ» ÇÑ´Ù 386
10.10 Telomerase negative mouse¿¡¼ tumor¿¡ ´ëÇÑ susceptibility (°¨¼ö¼º) 388
10.11 Telomerase negative mouse¿¡ ³ªÅ¸³ª´Â Çö»ó°ú ½ÇÁ¦ human cancer¿¡¼ ³ªÅ¸³ª´Â cancer ¹ß»ý ±âÀü 392
10.12 °³¿ä ¹× Àü¸Á 393
Key concept 397
Thought question 398
Additional reading 398
11Àå Multi-Step Tumorigenesis
11.1 ´ëºÎºÐÀÇ human cancer´Â ¼ö½Ê ³â¿¡ °ÉÃļ ¹ß´ÞÇÑ´Ù 400
11.2 Histopathology (Á¶Á÷º´¸®ÇÐ)´Â multi-step tumor formationÀÇ Áõ°Å¸¦ Á¦½ÃÇÑ´Ù 403
11.3 Colonic growth¿¡ µû¸¥ À¯ÀüÀû º¯È¿Í tumor progression 408
11.4 Multi-step tumor progression°ú familial polyposis ¹× field cancerization 412
11.5 TumorÀÇ ¹ß»ýÀº DarwinÀÇ ¹ýÄ¢À» µû¸£´Â °Íó·³ º¸Àδ٠413
11.6 Tumor stem cell (Á¾¾çÁٱ⼼Æ÷)°ú tumor progression eading
15Àå Crowd Control: Tumor Immunology¿Í Immunotherapy (¸é¿ªÄ¡·á) 15.1 ÀÎüÀÇ immune systemÀº º¹ÀâÇÑ °úÁ¤À» ÅëÇØ ¿ÜºÎ ħÀÔÀÚ¿Í ºñÁ¤»ó cellÀ» Á¦°ÅÇÑ´Ù 15.2 Adaptive immune response´Â antibody¸¦ »ý¼ºÇÑ´Ù 15.3 Adaptive immune response´Â cytotoxic cellÀ» Çü¼º½ÃŲ´Ù 15.4 Innate immune response´Â prior sensitizationÀ» ÇÊ¿ä·Î ÇÏÁö ¾Ê´Ù 15.5 Immune tolerance (¸é¿ª°ü¿ë)¸¦ ÅëÇÑ self¿Í non-self ±¸ºÐÀÇ Çʿ伺 15.6 Regulatory T cellÀº adaptive immune responseÀÇ À¯µµ¸¦ ÀúÇØÇÒ ¼ö ÀÖ´Ù 15.7 Immunosurveillance ÀÌ·ÐÀÌ Åº»ýÇßÀ¸³ª, °ð ÁÂÀýÀÇ °íÅëÀ» ´çÇÑ´Ù 15.8 À¯ÀüÀÚ º¯Çü mouse°¡ immunosurveillance theoryÀÇ ºÎÈ°À» À̲ø¾ú´Ù 15.9 »ç¶÷ÀÇ immune systemÀº ¿©·¯ cancer¸¦ ¾ø¾Ö´Â Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 15.10 Á¤»óÁ¶Á÷°ú neoplastic tissue°£ÀÇ ÀÛÀº Â÷ÀÌ·Î ÀÎÇØ immune systemÀÌ ±×µéÀ» ±¸ºÐÇÒ ¼ö ÀÖ´Ù 15.11 TumorÀÇ immune recognitionÀº tumor progression¿¡¼ ºñ±³Àû ´Ê°Ô ÀϾ٠15.12 Tumor-specific transplantation antigenÀº Á¾Á¾ °·ÂÇÑ ¸é¿ª ¹ÝÀÀÀ» À¯µµÇÑ´Ù 15.13 Tumor-associated transplantation antigenµµ anti-tumor immune response¸¦ À¯µµÇÑ´Ù 15.14 Cancer cellÀº tumor antigenÀÌ cell Ç¥¸é¿¡ displayµÇ´Â °ÍÀ» ¾ïÁ¦ÇÔÀ¸·Î½á immune detectionÀ» ÇÇÇÒ ¼ö ÀÖ´Ù 15.15 Cancer cellÀº NK cell¿¡ ÀÇÇÑ °ø°ÝÀ¸·ÎºÎÅÍ ÀÚ½ÅÀ» º¸È£ÇÑ´Ù 15.16 Cancer cellÀº immunocyte¿¡°Ô ¹Ý°ÝÀ» °¡ÇÑ´Ù 15.17 Cancer cellµéÀº immune systemÀÌ À¯µµÇÏ´Â ´Ù¾çÇÑ killing ¹æ½Ä¿¡ ´ëÇÏ¿© º»ÁúÀûÀ¸·Î ÀúÇ×·ÂÀ» °¡Áø´Ù 15.18 Cancer cellÀº lymphocyteÀÇ °ø°ÝÀ» ÇÇÇϱâ À§ÇØ regulatory T cellÀ» ºÒ·¯ ¸ðÀº´Ù 15.19 HerceptinÀÇ passive immunizationÀº breast cancer cellÀ» Á×À̴µ¥ ¾²ÀÏ ¼ö ÀÖ´Ù 15.20 AntibodyÀÇ passive immunizationÀº B-cell tumorÀÇ Ä¡·á¿¡ ¾²ÀÏ ¼ö ÀÖ´Ù 15.21 Passive immunizationÀº ÇÑ °³Ã¼·ÎºÎÅÍ ´Ù¸¥ °³Ã¼¿¡°Ô immunocyte¸¦ Àü´ÞÇÔÀ¸·Î½á ÀÌ·ç¾îÁø´Ù 15.22 Cancer¸¦ °ø°ÝÇϱâ À§ÇÏ¿© ȯÀÚÀÇ immune systemÀº mobilize (À̵¿) ÇÒ ¼ö ÀÖ´Ù 15.23 °³¿ä ¹× Àü¸Á Key Concept Thought question Additional reading
16Àå CancerÀÇ ÇÕ¸®ÀûÀÎ Ä¡·á¹ý 16.1 È¿°úÀûÀÎ Ä¡·áÁ¦ÀÇ °³¹ß ¹× ÀÓ»ó È°¿ëÀº Áúº´ÀÇ Á¤È®ÇÑ Áø´Ü¿¡ ´Þ·ÁÀÖ´Ù 16.2 ¼º°øÀûÀÎ Ç×¾ÏÁ¦µéÀº cancer cell·ÎºÎÅÍ ¸î °¡Áö ¹ÝÀÀµéÀ» ºÒ·¯ÀÏÀ¸Å³ ¼ö ÀÖ´Ù 16.3 cancer cell¿¡¼ ¼Õ»óµÈ ÀϺΠ´Ü¹éÁú¿¡ ´ëÇÑ ±â´ÉÀû °í·Á´Â Ç×¾ÏÁ¦ °³¹ß¿¡¼ È¿°úÀûÀÎ targeting ¹æ¹ýÀÌ´Ù 16.4 ´Ü¹éÁúÀÇ »ýÈÇÐÀûÀΠƯ¼ºÀº È¿°úÀûÀΠŸ°ÙµéÀ» °áÁ¤ÇÏ´Â Áß¿ä ¿ä¼ÒÀÌ´Ù 16.5 Á¦¾àÈÇÐÀÚµéÀº Æø³ÐÀº ¹üÀ§ÀÇ ÀáÀçÀû ¾à¹°µé¿¡ ´ëÇÑ »ýÈÇÐÀû Ư¼ºÀ» âÃâÇÏ°í °ËÅäÇÒ ¼ö ÀÖ´Ù 16.6 ½Å¾à Èĺ¸¹°ÁúµéÀº °³Ã¼ ¼öÁØ À¯¿ë¼º ÃøÁ¤ÀÇ Ã¹ ´Ü°è·Î¼ ¼¼Æ÷ »ó¿¡¼ °ËÁõµÇ¾î¾ß ÇÑ´Ù 16.7 ½ÇÇ赿¹°¿¡¼ÀÇ ¾à¹° ÀÛ¿ë ¿¬±¸´Â ÀüÀÓ»óÀÇ Çʼö °úÁ¤ÀÌ´Ù 16.8 Àå·¡¼º ÀÖ´Â Èĺ¸¾à¹°Àº ÀÓ»ó I»ó¿¡¼ Àΰ£À» ´ë»óÀ¸·ÎÇÑ ¾ö°ÝÇÏ°í ±¤¹üÀ§ÇÑ ÀÓ»ó½ÇÇèÀ» ¹Þ¾Æ¾ß ÇÑ´Ù 16.9 ÀÓ»ó II»ó°ú III»ó ½ÃÇèÀº ÀÓ»óÀû È¿ÇèÀ» º¸ÀÌ´Â È®½ÇÇÑ ÀûÀÀÁõµéÀ» Á¦°øÇÑ´Ù 16.10 Á¾¾çÀº óÀ½¿¡ È¿°úÀûÀÌ´ø Ä¡·á¿¡ ³»¼ºÀ» º¸ÀÌ´Â °æ¿ì°¡ ¸¹´Ù 16.11 GleevecÀÇ °³¹ßÀº ¿©Å¸ ´Ù¼öÀÇ Ç¥ÀûÁöÇâÀû ¾à¹°µéÀÇ °³¹ßÀ» ¿ëÀÌÇÏ°Ô Çß´Ù 16.12 EGF receptor (¼ö¿ëü)ÀÇ antagonist (±æÇ×Á¦)µéÀº ´Ù¾çÇÑ ¾ÏÁ¾¿¡ À¯¿ëÇÏ°Ô »ç¿ëÇÒ ¼ö ÀÖ´Ù 16.13 Proteasome ÀúÇØÁ¦´Â ¿¹»óÄ¡ ¸øÇÑ Ä¡·á È¿°ú¸¦ °¡Á®¿Ô´Ù 16.14 Sheep teratogenÀº È¿´ÉÀÌ ¶Ù¾î³ Ç×¾ÏÁ¦·Î ÀÌ¿ëµÉ ¼ö ÀÖ´Ù 16.15 ¼¼Æ÷ »ý¸®ÀÇ master regulatorÀÎ mTOR´Â Ç×¾ÏÄ¡·á¸¦ À§ÇÑ ¸Å·ÂÀûÀΠŸ°ÙÀÌ´Ù 16.16 °³¿ä ¹× Àü¸Á : ¾Õ³¯ÀÇ µµÀü°ú ±âȸ Key concept Thought question Additional reading ±×¸®°í DarwinÀÇ ¸ðµ¨ 416
11.7 Clonal successionÀÇ liner path´Â ¾ÏÀ» Áö³ªÄ¡°Ô ´Ü¼øȽÃŲ´Ù 420
11.8 Darwin model¿¡ ´ëÇÑ ½ÇÇèÀû Áõ¸íÀÇ ³Á¡ 423
11.9 Single mutated gene (´ÜÀÏ À¯ÀüÀû º¯ÀÌ)Àº normal cellÀ» transformation ½ÃÅ°Áö ¸øÇÑ´Ù 424
11.10 TransformationÀº Àû¾îµµ 2?3 °³ÀÇ À¯ÀüÀû º¯ÀÌ°¡ ÇÊ¿äÇÏ´Ù 427
11.11 Transgenic mouse¸¦ ÀÌ¿ëÇÑ oncogeneÀÇ »óÈ£ÀÛ¿ë ¹× multi-step cell transformation ¿¬±¸ 429
11.12 Human cellÀº immortalization°ú transformation¿¡ °ÇÑ ÀúÇ×¼ºÀÌ ÀÖ´Ù 431
11.13 Nonmutagenic carcinogen (¼¼Æ÷ ¼ºÀå ÃËÁø ¹°Áú µî)¿¡ ÀÇÇÑ tumorigenesis 435
11.14 Tumor promoter·Î¼ÀÇ µ¶¼º ¹°Áú°ú ¼ºÀå ÃËÁø ¹°Áú (toxic and mitogenic agent) 438
11.15 Human°ú ½ÇÇè¿ë mouse¿¡¼ tumor promoter·Î¼ÀÇ chronic inflammation (¸¸¼º ¿°Áõ) 441
11.16 Inflammation °ü·Ã tumor promotionÀÇ signaling pathway 444
11.17 Tumor promoterÀº tumor progressionÀÇ ¼Óµµ¸¦ Á¶ÀýÇÏ´Â Áß¿äÇÑ °áÁ¤ ÀÎÀÚÀÌ´Ù 452
11.18 °³¿ä ¹× Àü¸Á 453
Key concept 460
Thought question 461
Additional reading 461
12Àå Genomic IntegrityÀÇ À¯Áö¿Í CancerÀÇ ¹ß»ý
12.1 Tissue´Â mutationÀÇ ÃàÀûÀÌ Àß ÀϾÁö ¾Êµµ·Ï ±¸¼ºµÇ¾î ÀÖ´Ù 464
12.2 Stem cellÀº cancer¸¦ À¯µµÇÏ´Â mutagenesisÀÇ targetÀ¸·Î º¸Àδ٠466
12.3 Apoptosis¿Í drug pump, ±×¸®°í DNA replicationÀÇ mechanismÀº mutant stem cellÀÌ tissue¿¡ ÃàÀûµÇ´Â °ÍÀ» ¾ïÁ¦ÇÑ´Ù 470
12.4 ¼¼Æ÷ÀÇ genomeÀº DNA replication °úÁ¤¿¡¼ ¹ß»ýÇÏ´Â ¿À·ù·ÎºÎÅÍ À§ÇùÀ» ¹Þ´Â´Ù 475
12.5 ¼¼Æ÷ÀÇ genomeÀº endogenous biochemical process·ÎºÎÅÍ ²÷ÀÓ¾øÀÌ °ø°ÝÀ» ¹Þ´Â´Ù 479
12.6 ¼¼Æ÷ÀÇ genomeÀº ¶§¶§·Î exogenous mutagen°ú ±×µéÀÇ metabolite·ÎºÎÅÍ °ø°ÝÀ» ¹Þ´Â´Ù 484
12.7 ¼¼Æ÷´Â mutagenÀÇ °ø°ÝÀ¸·ÎºÎÅÍ DNA¸¦ º¸È£Çϱâ À§ÇØ ´Ù¾çÇÑ ¹æ¾î ±âÀÛÀ» »ç¿ëÇÑ´Ù 490
12.8 Repair enzymeÀº mutagen¿¡ ÀÇÇØ º¯ÇüµÈ DNA¸¦ °íÄ£´Ù 493
12.9 Nucleotide excision repair¿Í base excision repair ±×¸®°í mismatch repairÀÇ ±âÀü¿¡ ¹ß»ýÇÑ inherited defect´Â specific cancer susceptibility syndromeÀ» À¯¹ßÇÑ´Ù 499
12.10 ´Ù¾çÇÑ Á¾·ùÀÇ DNA repair ±âÀÛ¿¡ »ý±ä defect´Â ¾ÆÁ÷ ¹àÇôÁöÁö ¾ÊÀº ±âÀÛÀ» ÅëÇØ cancer susceptibility¸¦ Áõ°¡½ÃŲ´Ù 505
12.11 Cancer cellÀÇ karyotypeÀº chromosome ±¸Á¶ÀÇ º¯Çü¿¡ ÀÇÇØ ÀÚÁÖ ¹Ù²ï´Ù 510
12.12 Cancer cellÀÇ karyotypeÀº chromosome ¼öÀÇ º¯Çü¿¡ ÀÇÇØ ÀÚÁÖ ¹Ù²ï´Ù 511
12.13 °³¿ä ¹× Àü¸Á 517
Key concept 524
Thought question 525
Additional reading 525
13Àå Dialogue (´ëÈ)´Â Monologue (µ¶¹é)¸¦ ´ëüÇÑ´Ù : Heterotypic Interaction°ú AngiogenesisÀÇ »ý¹°ÇÐ
13.1 Á¤»ó »óÇÇ Á¶Á÷°ú Á¾¾ç »óÇÇ Á¶Á÷Àº ¼·Î ÀÇÁ¸ÇÏ´Â ¼¼Æ÷ À¯ÇüÀ¸·ÎºÎÅÍ Çü¼ºµÈ´Ù 528
13.2 Cancer cell lineÀ» Çü¼ºÇÏ´Â ¼¼Æ÷´Â heterotypic interaction ¾øÀÌ ¹ß´ÞÇÏ°í human tumor ³»¿¡ ÀÖ´Â ¼¼Æ÷ÀÇ Çൿ¿¡¼ ¹þ¾î³´Ù 536
13.3 Tumor´Â Ä¡·áµÇÁö ¾ÊÀº »óóÁ¶Á÷°ú °øÅëÁ¡ÀÌ ÀÖ´Ù 537
13.4 Stromal cellÀº tumorigenesisÀÇ active contributorÀÌ´Ù 548
13.5 Macrophage´Â È°¼ºÈµÈ tumor-associated stroma¿¡¼ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 551
13.6 Endothelial cell°ú À̵éÀÌ ¸¸µå´Â vesselÀº tumor·Î ÇÏ¿©±Ý circulation¿¡ ½±°Ô µé¾î°¥ ¼ö ÀÖ°Ô ÇÑ´Ù 556
13.7 Angiogenic switchÀÇ ¹Îø¼ºÀº Á¾¾ç Áõ½Ä¿¡ ÇʼöÀûÀÌ´Ù 562
13.8 Angiogenic switch´Â ³ôÀº º¹ÇÕü °úÁ¤À» ½ÃÀÛÇÏ°Ô ÇÑ´Ù 567
13.9 Ç÷°ü½Å»ýÀº »ý¸®Àû ÀúÇع°¿¡ ÀÇÇØ ¾ïÁ¦µÈ´Ù 571
13.10 ¾î¶² anti-angiogenesis therapyµéÀº cancerÀÇ Ä¡·á¿¡ ´ëÇÑ Àü¸ÁÀ» ¹à°Ô ÇØÁØ´Ù 574
13.11 °³¿ä¿Í Àü¸Á 581
Key concept 585
Thought question 585
Additional reading 586
14Àå Cancer CellÀÇ À̵¿ : Invasion (ħÅõ)°ú Metastasis (ÀüÀÌ)
14.1 Cancer cellÀÌ primary tumor·ÎºÎÅÍ metastasis°¡ °¡´ÉÇÑ Àå¼Ò·Î À̵¿Çϱâ À§Çؼ´Â º¹ÀâÇÑ »ý¹°ÇÐÀû °úÁ¤À» °ÅÃÄ¾ß ÇÑ´Ù 589
14.2 Colonization (±ºÁýÀ» ÀÌ·ç´Â °Í)Àº invasion-metastasis cascade¿¡¼ °¡Àå º¹ÀâÇÏ°í ¾î·Á¿î ´Ü°èÀÌ´Ù 594
14.3 Epithelial-mesenchymal transition°ú ÀÌ¿Í °ü·ÃµÈ E-cadherinÀÇ ¹ßÇöÀÌ ¼Ò½ÇµÇ¸é carcinoma cellÀº invasiveÇÏ°Ô µÈ´Ù 597
14.4 Epithelial-mesenchymal transitionÀº stromal signal¿¡ ÀÇÇØ À¯µµµÇ±âµµ ÇÑ´Ù 605
14.5 EMT´Â embryogenesisÀÇ ÁÖ¿ä ´Ü°è¸¦ Á¶ÀýÇÏ´Â transcription factorµé¿¡ ÀÇÇÏ¿© program µÈ´Ù 615
14.6 Extracellular proteaseµéÀÌ invasiveness¿¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 621
14.7 Small Ras-like GTPase´Â adhesion°ú ¼¼Æ÷ÀÇ ¸ð¾ç, ±×¸®°í ¼¼Æ÷ÀÇ motility (¿îµ¿¼º)¸¦ Á¶ÀýÇÑ´Ù 624
14.8 ÀüÀÌÇÏ´Â ¼¼Æ÷´Â lymphatic vesselÀ» ÀÌ¿ëÇÏ¿© primary tumor·ÎºÎÅÍ ÆÛÁ® ³ª°£´Ù 631
14.9 ÆÛÁ® ³ª°£ cancer cellÀÌ ¾î¶² ±â°ü¿¡¼ ÀüÀ̸¦ Çü¼ºÇÒÁö¸¦ °áÁ¤ÇÏ´Â µ¥¿¡´Â ¸¹Àº ¿ä¼Ò°¡ °ü¿©ÇÑ´Ù 634
14.10 »À·Î ÀüÀ̵ǷÁ¸é osteoblast (Á¶°ñ¼¼Æ÷(ðãÍéá¬øà))¿Í osteoclast (ÆÄ°ñ(÷òÍé)¼¼Æ÷)ÀÇ subversionÀÌ ÇÊ¿äÇÏ´Ù 638
14.11 Metastasis suppressor gene (ÀüÀ̾ïÁ¦ À¯ÀüÀÚ)µéÀº metastatic phenotype (ÀüÀÌ Ç¥ÇöÇü)À» Á¶ÀýÇÑ´Ù 642
14.12 Occult (À°¾ÈÀ¸·Î º¸ÀÌÁö ¾Ê´Â) micrometastasis°¡ ¾Ï ȯÀÚÀÇ Àå±â »ýÁ¸À» À§ÇùÇÑ´Ù 645
14.13 °³¿ä ¹× Àü¸Á 646
Key concept 652
Thought question 653
Additional reading 653
15Àå Crowd Control: Tumor Immunology¿Í Immunotherapy (¸é¿ªÄ¡·á)
15.1 ÀÎüÀÇ immune systemÀº º¹ÀâÇÑ °úÁ¤À» ÅëÇØ ¿ÜºÎ ħÀÔÀÚ¿Í ºñÁ¤»ó cellÀ» Á¦°ÅÇÑ´Ù 656
15.2 Adaptive immune response´Â antibody¸¦ »ý¼ºÇÑ´Ù 659
15.3 Adaptive immune response´Â cytotoxic cellÀ» Çü¼º½ÃŲ´Ù 663
15.4 Innate immune response´Â prior sensitizationÀ» ÇÊ¿ä·Î ÇÏÁö ¾Ê´Ù 666
15.5 Immune tolerance (¸é¿ª°ü¿ë)¸¦ ÅëÇÑ self¿Í non-self ±¸ºÐÀÇ Çʿ伺 668
15.6 Regulatory T cellÀº adaptive immune responseÀÇ À¯µµ¸¦ ÀúÇØÇÒ ¼ö ÀÖ´Ù 669
15.7 Immunosurveillance ÀÌ·ÐÀÌ Åº»ýÇßÀ¸³ª, °ð ÁÂÀýÀÇ °íÅëÀ» ´çÇÑ´Ù 669
15.8 À¯ÀüÀÚ º¯Çü mouse°¡ immunosurveillance theoryÀÇ ºÎÈ°À» À̲ø¾ú´Ù 673
15.9 »ç¶÷ÀÇ immune systemÀº ¿©·¯ cancer¸¦ ¾ø¾Ö´Â Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù 675
15.10 Á¤»óÁ¶Á÷°ú neoplastic tissue°£ÀÇ ÀÛÀº Â÷ÀÌ·Î ÀÎÇØ immune systemÀÌ ±×µéÀ» ±¸ºÐÇÒ ¼ö ÀÖ´Ù 681
15.11 TumorÀÇ immune recognitionÀº tumor progression¿¡¼ ºñ±³Àû ´Ê°Ô ÀϾ٠683
15.12 Tumor-specific transplantation antigenÀº Á¾Á¾ °·ÂÇÑ ¸é¿ª ¹ÝÀÀÀ» À¯µµÇÑ´Ù 685
15.13 Tumor-associated transplantation antigenµµ anti-tumor immune response¸¦ À¯µµÇÑ´Ù 687
15.14 Cancer cellÀº tumor antigenÀÌ cell Ç¥¸é¿¡ displayµÇ´Â °ÍÀ» ¾ïÁ¦ÇÔÀ¸·Î½á immune detectionÀ» ÇÇÇÒ ¼ö ÀÖ´Ù 689
15.15 Cancer cellÀº NK cell¿¡ ÀÇÇÑ °ø°ÝÀ¸·ÎºÎÅÍ ÀÚ½ÅÀ» º¸È£ÇÑ´Ù 695
15.16 Cancer cellÀº immunocyte¿¡°Ô ¹Ý°ÝÀ» °¡ÇÑ´Ù 697
15.17 Cancer cellµéÀº immune systemÀÌ À¯µµÇÏ´Â ´Ù¾çÇÑ killing ¹æ½Ä¿¡ ´ëÇÏ¿© º»ÁúÀûÀ¸·Î ÀúÇ×·ÂÀ» °¡Áø´Ù 701
15.18 Cancer cellÀº lymphocyteÀÇ °ø°ÝÀ» ÇÇÇϱâ À§ÇØ regulatory T cellÀ» ºÒ·¯ ¸ðÀº´Ù 703
15.19 HerceptinÀÇ passive immunizationÀº breast cancer cellÀ» Á×À̴µ¥ ¾²ÀÏ ¼ö ÀÖ´Ù 704
15.20 AntibodyÀÇ passive immunizationÀº B-cell tumorÀÇ Ä¡·á¿¡ ¾²ÀÏ ¼ö ÀÖ´Ù 708
15.21 Passive immunizationÀº ÇÑ °³Ã¼·ÎºÎÅÍ ´Ù¸¥ °³Ã¼¿¡°Ô immunocyte¸¦ Àü´ÞÇÔÀ¸·Î½á ÀÌ·ç¾îÁø´Ù 713
15.22 Cancer¸¦ °ø°ÝÇϱâ À§ÇÏ¿© ȯÀÚÀÇ immune systemÀº mobilize (À̵¿) ÇÒ ¼ö ÀÖ´Ù 714
15.23 °³¿ä ¹× Àü¸Á 720
Key Concept 722
Thought question 724
Additional reading 724
16Àå CancerÀÇ ÇÕ¸®ÀûÀÎ Ä¡·á¹ý
16.1 È¿°úÀûÀÎ Ä¡·áÁ¦ÀÇ °³¹ß ¹× ÀÓ»ó È°¿ëÀº Áúº´ÀÇ Á¤È®ÇÑ Áø´Ü¿¡ ´Þ·ÁÀÖ´Ù 727
16.2 ¼º°øÀûÀÎ Ç×¾ÏÁ¦µéÀº cancer cell·ÎºÎÅÍ ¸î °¡Áö ¹ÝÀÀµéÀ» ºÒ·¯ÀÏÀ¸Å³ ¼ö ÀÖ´Ù 732
16.3 cancer cell¿¡¼ ¼Õ»óµÈ ÀϺΠ´Ü¹éÁú¿¡ ´ëÇÑ ±â´ÉÀû °í·Á´Â Ç×¾ÏÁ¦ °³¹ß¿¡¼ È¿°úÀûÀÎ targeting ¹æ¹ýÀÌ´Ù 734
16.4 ´Ü¹éÁúÀÇ »ýÈÇÐÀûÀΠƯ¼ºÀº È¿°úÀûÀΠŸ°ÙµéÀ» °áÁ¤ÇÏ´Â Áß¿ä ¿ä¼ÒÀÌ´Ù 737
16.5 Á¦¾àÈÇÐÀÚµéÀº Æø³ÐÀº ¹üÀ§ÀÇ ÀáÀçÀû ¾à¹°µé¿¡ ´ëÇÑ »ýÈÇÐÀû Ư¼ºÀ» âÃâÇÏ°í °ËÅäÇÒ ¼ö ÀÖ´Ù 744
16.6 ½Å¾à Èĺ¸¹°ÁúµéÀº °³Ã¼ ¼öÁØ À¯¿ë¼º ÃøÁ¤ÀÇ Ã¹ ´Ü°è·Î¼ ¼¼Æ÷ »ó¿¡¼ °ËÁõµÇ¾î¾ß ÇÑ´Ù 747
16.7 ½ÇÇ赿¹°¿¡¼ÀÇ ¾à¹° ÀÛ¿ë ¿¬±¸´Â ÀüÀÓ»óÀÇ Çʼö °úÁ¤ÀÌ´Ù 748
16.8 Àå·¡¼º ÀÖ´Â Èĺ¸¾à¹°Àº ÀÓ»ó I»ó¿¡¼ Àΰ£À» ´ë»óÀ¸·ÎÇÑ ¾ö°ÝÇÏ°í ±¤¹üÀ§ÇÑ ÀÓ»ó½ÇÇèÀ» ¹Þ¾Æ¾ß ÇÑ´Ù 751
16.9 ÀÓ»ó II»ó°ú III»ó ½ÃÇèÀº ÀÓ»óÀû È¿ÇèÀ» º¸ÀÌ´Â È®½ÇÇÑ ÀûÀÀÁõµéÀ» Á¦°øÇÑ´Ù 752
16.10 Á¾¾çÀº óÀ½¿¡ È¿°úÀûÀÌ´ø Ä¡·á¿¡ ³»¼ºÀ» º¸ÀÌ´Â °æ¿ì°¡ ¸¹´Ù 755
16.11 GleevecÀÇ °³¹ßÀº ¿©Å¸ ´Ù¼öÀÇ Ç¥ÀûÁöÇâÀû ¾à¹°µéÀÇ °³¹ßÀ» ¿ëÀÌÇÏ°Ô Çß´Ù 757
16.12 EGF receptor (¼ö¿ëü)ÀÇ antagonist (±æÇ×Á¦)µéÀº ´Ù¾çÇÑ ¾ÏÁ¾¿¡ À¯¿ëÇÏ°Ô »ç¿ëÇÒ ¼ö ÀÖ´Ù 765
16.13 Proteasome ÀúÇØÁ¦´Â ¿¹»óÄ¡ ¸øÇÑ Ä¡·á È¿°ú¸¦ °¡Á®¿Ô´Ù 769
16.14 Sheep teratogenÀº È¿´ÉÀÌ ¶Ù¾î³ Ç×¾ÏÁ¦·Î ÀÌ¿ëµÉ ¼ö ÀÖ´Ù 776
16.15 ¼¼Æ÷ »ý¸®ÀÇ master regulatorÀÎ mTOR´Â Ç×¾ÏÄ¡·á¸¦ À§ÇÑ ¸Å·ÂÀûÀΠŸ°ÙÀÌ´Ù 782
16.16 °³¿ä ¹× Àü¸Á : ¾Õ³¯ÀÇ µµÀü°ú ±âȸ 787
Key concept 794
Thought question 795
Additional reading 795
Abbreviations
Glossary
Index
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·Î¹öÆ® ¿ÍÀιö±×(Robert A. Weinberg) [Àú]
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¸Å»çÃß¼¼Ã÷ °ø°ú ´ëÇп¡¼ ¹Ú»ç ÇÐÀ§¸¦ ¹Þ¾Ò´Ù. ÇöÀç ¸Å»çÃß¼¼Ã÷ °ø°ú ´ëÇÐ ºÎ¼³ ÈÀÌÆ®Çìµå ¿¬±¸¼Ò »ý¹°ÀÇÇÐ ±³½Ç ±³¼ö·Î ÀçÁ÷ ÁßÀÌ´Ù. ±×ÀÇ ¿¬±¸½ÇÀº Á¤»ó ¼¼Æ÷¸¦ ¾Ï¼¼Æ÷¸¦ ¹Ù²Ù´Â ¾Ï À¯ÀüÀÚ°¡ ÀÖÀ½°ú ±× ¸ÞÄ¿´ÏÁòÀ» óÀ½À¸·Î ¹àÇô³» ¾Ï Ä¡·áÀÇ »õ·Î¿î Àü±â¸¦ ¸¶·ÃÇß´Ù. ¿ÍÀιö±×´Â ÀÌ ¿¬±¸ ¾÷ÀûÀ¸·Î ¹Ì±¹ ±¹°¡ °úÇÐ ÈÆÀå µî ¿©·¯ °úÇлóÀ» ¹Þ¾Ò´Ù.
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ÀÌÇÑ¿õ [Àú]
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Àüü 0°³ÀÇ ±¸¸ÅÈıⰡ ÀÖ½À´Ï´Ù.
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