惡性轉化

惡性轉化（Malignant transformation）是指細胞或組織產生一系列遺傳學上的變化，並獲得惡性增殖（無限增殖）和轉移能力的過程。惡性轉化在體內可能發生於正常細胞或組織中，也可能發生於良性腫瘤中。發生惡性轉化的細胞或組織最終可能會發展為惡性腫瘤^[1]^[2]。另外，研究人員為了方便研究，也可能在體外使用特殊技術方法對細胞進行惡性轉化^[3]。

不健康的生活習慣，比如吸菸、不健康的飲食、酗酒、混亂的性生活等可能造成體內的惡性轉化，產生惡性腫瘤。此外，病毒、細菌的感染也可能造成體內細胞或組織的惡性轉化^[4]^[5]^[6]^[7]。一定水平的重金屬，如鎳、鎘也可造成惡性轉化^[8]^[9]^[10]^[11]。

惡性轉化過程中，細胞會發生一系列遺傳學上的變化^[2]。

基因突變是惡性轉化的成因之一，抑癌基因和（或）原癌基因的突變會造成惡性轉化。根據統計，乳腺癌組織中平均基因突變數達20,000處以上^[12]，普通的惡性黑色素瘤組織中平均基因突變數則達到80,000處^[13]。

此外，表觀遺傳學上的改變也可能造成惡性轉化。比如，在惡性轉化過程中，部分與DNA修復相關的基因或其他基因可能會因啓動子區域過甲基化而發生轉錄水平上的沉默^[14]^[15]^[16]^[17]。另外，在惡性轉化過程中，RNA干擾等轉錄後調控機制也可能會發生改變。比如，乳腺癌組織中的多種miRNA會因為啓動子發生過甲基化而停止表達，後續的RNA干擾也因此而停止進行^[18]。

細胞生物學研究者為了方便研究，可能會在體外（in vitro）使用病毒感染等方法對動物細胞進行惡性轉化，獲得永生化細胞系（英语：Immortalised cell line）。比如HEK 293細胞就是使用5型腺病毒DNA片段惡性轉化的人胚腎細胞。另外，在體外進行惡性轉化對研究體內（in vivo）的惡性轉化過程也有一定助益^[19]^[3]^[20]。

惡性腫瘤
永生化細胞系（英语：Immortalised cell line）

[1]
MALIGNANT TRANSFORMATION. [2018-03-03]. （原始内容存档于2016-12-30）.
[2]
Tsz-Kwong Man; et al. Chapter 15 – Genomic and Proteomic Profiling of Osteosarcoma. Bone Cancer: Progression and Therapeutic Approaches. 2010: 181–192.
[3]
IAN DE G. MITCHELL; ROBERT D. COMBES. In Vitro Genotoxicity and Cell Transformation Assessment. In Vitro Methods in Pharmaceutical Research. 1997: 317–352.
[4]
Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 1981, 66 (6): 1191–308. PMID 7017215. doi:10.1093/jnci/66.6.1192.
[5]
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[6]
Song M, Giovannucci EL. RE: Doll and Peto's Quantitative Estimates of Cancer Risks: Holding Generally True for 35 Years. J. Natl. Cancer Inst. 2015, 107 (10): djv240. PMID 26271254. doi:10.1093/jnci/djv240.
[7]
Correa P. Helicobacter pylori and gastric carcinogenesis. Am. J. Surg. Pathol. 1995,. 19 Suppl 1: S37–43. PMID 7762738.
[8]
Nawrot TS, Martens DS, Hara A, Plusquin M, Vangronsveld J, Roels HA, Staessen JA. Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence. Cancer Causes Control. 2015, 26 (9): 1281–8. PMID 26109463. doi:10.1007/s10552-015-0621-5.
[9]
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[10]
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[11]
Ji W, Yang L, Yuan J, Yang L, Zhang M, Qi D, Duan X, Xuan A, Zhang W, Lu J, Zhuang Z, Zeng G. MicroRNA-152 targets DNA methyltransferase 1 in NiS-transformed cells via a feedback mechanism. Carcinogenesis. 2013, 34 (2): 446–53. PMID 23125218. doi:10.1093/carcin/bgs343.
[12]
Yost SE; Smith EN; Schwab RB; Bao L; Jung H; Wang X; Voest E; Pierce JP; Messer K; Parker BA; Harismendy O; Frazer KA. Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens. Nucleic Acids Res. August 2012, 40 (14): e107. PMC 3413110 . PMID 22492626. doi:10.1093/nar/gks299.
[13]
Berger MF; et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. May 2012, 485 (7399): 502–6. PMC 3367798 . PMID 22622578. doi:10.1038/nature11071.
[14]
Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R, Bird AP. Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet. 2010, 6 (9): e1001134. PMC 2944787 . PMID 20885785. doi:10.1371/journal.pgen.1001134.
[15]
Wei J, Li G, Dang S, Zhou Y, Zeng K, Liu M. Discovery and Validation of Hypermethylated Markers for Colorectal Cancer. Dis. Markers. 2016, 2016: 2192853. PMC 4963574 . PMID 27493446. doi:10.1155/2016/2192853.
[16]
Beggs AD, Jones A, El-Bahrawy M, El-Bahwary M, Abulafi M, Hodgson SV, Tomlinson IP. Whole-genome methylation analysis of benign and malignant colorectal tumours. J. Pathol. 2013, 229 (5): 697–704. PMC 3619233 . PMID 23096130. doi:10.1002/path.4132.
[17]
Carol Bernstein and Harris Bernstein (2015). Epigenetic Reduction of DNA Repair in Progression to Cancer, Advances in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-2209-8, InTech, Available from: http://www.intechopen.com/books/advances-in-dna-repair/epigenetic-reduction-of-dna-repair-in-progression-to-cancer （页面存档备份，存于互联网档案馆）
[18]
Vrba, L; Muñoz-Rodríguez, JL; Stampfer, MR; Futscher, BW. miRNA Gene Promoters Are Frequent Targets of Aberrant DNA Methylation in Human Breast Cancer.. PLOS ONE. 2013, 8 (1): e54398. PMC 3547033 . PMID 23342147. doi:10.1371/journal.pone.0054398.
[19]
Paul H. Black. Malignant Transformation in Vitro by Oncogenic Viruses. JAMA. 1968;206(6):1258-1262.
[20]
Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. July 1977, 36 (1): 59–74. PMID 886304. doi:10.1099/0022-1317-36-1-59.^{[永久失效連結]}

[1] [1]
MALIGNANT TRANSFORMATION. [2018-03-03]. （原始内容存档于2016-12-30）.

[Man2010-2] [2]
Tsz-Kwong Man; et al. Chapter 15 – Genomic and Proteomic Profiling of Osteosarcoma. Bone Cancer: Progression and Therapeutic Approaches. 2010: 181–192.

[MITCHELL1997-3] [3]
IAN DE G. MITCHELL; ROBERT D. COMBES. In Vitro Genotoxicity and Cell Transformation Assessment. In Vitro Methods in Pharmaceutical Research. 1997: 317–352.

[Doll-4] [4]
Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 1981, 66 (6): 1191–308. PMID 7017215. doi:10.1093/jnci/66.6.1192.

[Blot-5] [5]
Blot WJ, Tarone RE. Doll and Peto's quantitative estimates of cancer risks: holding generally true for 35 years. J. Natl. Cancer Inst. 2015, 107 (4): djv044. PMID 25739419. doi:10.1093/jnci/djv044.

[pmid26271254-6] [6]
Song M, Giovannucci EL. RE: Doll and Peto's Quantitative Estimates of Cancer Risks: Holding Generally True for 35 Years. J. Natl. Cancer Inst. 2015, 107 (10): djv240. PMID 26271254. doi:10.1093/jnci/djv240.

[pmid7762738-7] [7]
Correa P. Helicobacter pylori and gastric carcinogenesis. Am. J. Surg. Pathol. 1995,. 19 Suppl 1: S37–43. PMID 7762738.

[pmid26109463-8] [8]
Nawrot TS, Martens DS, Hara A, Plusquin M, Vangronsveld J, Roels HA, Staessen JA. Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence. Cancer Causes Control. 2015, 26 (9): 1281–8. PMID 26109463. doi:10.1007/s10552-015-0621-5.

[pmid24040994-9] [9]
Cohen SM, Arnold LL, Beck BD, Lewis AS, Eldan M. Evaluation of the carcinogenicity of inorganic arsenic. Crit. Rev. Toxicol. 2013, 43 (9): 711–52. PMID 24040994. doi:10.3109/10408444.2013.827152.

[pmid23314041-10] [10]
Bhattacharjee P, Banerjee M, Giri AK. Role of genomic instability in arsenic-induced carcinogenicity. A review. Environ Int. 2013, 53: 29–40. PMID 23314041. doi:10.1016/j.envint.2012.12.004.

[pmid23125218-11] [11]
Ji W, Yang L, Yuan J, Yang L, Zhang M, Qi D, Duan X, Xuan A, Zhang W, Lu J, Zhuang Z, Zeng G. MicroRNA-152 targets DNA methyltransferase 1 in NiS-transformed cells via a feedback mechanism. Carcinogenesis. 2013, 34 (2): 446–53. PMID 23125218. doi:10.1093/carcin/bgs343.

[pmid22492626-12] [12]
Yost SE; Smith EN; Schwab RB; Bao L; Jung H; Wang X; Voest E; Pierce JP; Messer K; Parker BA; Harismendy O; Frazer KA. Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens. Nucleic Acids Res. August 2012, 40 (14): e107. PMC 3413110 . PMID 22492626. doi:10.1093/nar/gks299.

[pmid22622578-13] [13]
Berger MF; et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. May 2012, 485 (7399): 502–6. PMC 3367798 . PMID 22622578. doi:10.1038/nature11071.

[Illingworth-14] [14]
Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R, Bird AP. Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet. 2010, 6 (9): e1001134. PMC 2944787 . PMID 20885785. doi:10.1371/journal.pgen.1001134.

[pmid27493446-15] [15]
Wei J, Li G, Dang S, Zhou Y, Zeng K, Liu M. Discovery and Validation of Hypermethylated Markers for Colorectal Cancer. Dis. Markers. 2016, 2016: 2192853. PMC 4963574 . PMID 27493446. doi:10.1155/2016/2192853.

[Beggs-16] [16]
Beggs AD, Jones A, El-Bahrawy M, El-Bahwary M, Abulafi M, Hodgson SV, Tomlinson IP. Whole-genome methylation analysis of benign and malignant colorectal tumours. J. Pathol. 2013, 229 (5): 697–704. PMC 3619233 . PMID 23096130. doi:10.1002/path.4132.

[Bernstein2015-17] [17]
Carol Bernstein and Harris Bernstein (2015). Epigenetic Reduction of DNA Repair in Progression to Cancer, Advances in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-2209-8, InTech, Available from: http://www.intechopen.com/books/advances-in-dna-repair/epigenetic-reduction-of-dna-repair-in-progression-to-cancer （页面存档备份，存于互联网档案馆）

[18] [18]
Vrba, L; Muñoz-Rodríguez, JL; Stampfer, MR; Futscher, BW. miRNA Gene Promoters Are Frequent Targets of Aberrant DNA Methylation in Human Breast Cancer.. PLOS ONE. 2013, 8 (1): e54398. PMC 3547033 . PMID 23342147. doi:10.1371/journal.pone.0054398.

[19] [19]
Paul H. Black. Malignant Transformation in Vitro by Oncogenic Viruses. JAMA. 1968;206(6):1258-1262.

[pmid886304-20] [20]
Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. July 1977, 36 (1): 59–74. PMID 886304. doi:10.1099/0022-1317-36-1-59.^{[永久失效連結]}

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[20]

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惡性轉化

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成因

機制

體外惡性轉化

參見

参考文献