恶性转化
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/7/73/Cancer_requires_multiple_mutations_from_NIH.png/220px-Cancer_requires_multiple_mutations_from_NIH.png)
恶性转化(Malignant transformation)是指细胞或组织产生一系列遗传学上的变化,并获得恶性增殖(无限增殖)和转移能力的过程。恶性转化在体内可能发生于正常细胞或组织中, 也可能发生于良性肿瘤中。发生恶性转化的细胞或组织最终可能会发展为恶性肿瘤[1][2]。另外,研究人员为了方便研究,也可能在体外使用特殊技术方法对细胞进行恶性转化[3]。
成因
不健康的生活习惯,比如吸烟、不健康的饮食、酗酒、混乱的性生活等可能造成体内的恶性转化,产生恶性肿瘤。此外,病毒、细菌的感染也可能造成体内细胞或组织的恶性转化[4][5][6][7]。一定水平的重金属,如镍、镉也可造成恶性转化[8][9][10][11]。
机制
恶性转化过程中,细胞会发生一系列遗传学上的变化[2]。
基因突变是恶性转化的成因之一,抑癌基因和(或)原癌基因的突变会造成恶性转化。根据统计,乳腺癌组织中平均基因突变数达20,000处以上[12],普通的恶性黑色素瘤组织中平均基因突变数则达到80,000处[13]。
此外,表观遗传学上的改变也可能造成恶性转化。比如,在恶性转化过程中,部分与DNA修复相关的基因或其他基因可能会因启动子区域过甲基化而发生转录水平上的沉默[14][15][16][17]。另外,在恶性转化过程中,RNA干扰等转录后调控机制也可能会发生改变。比如,乳腺癌组织中的多种miRNA会因为启动子发生过甲基化而停止表达,后续的RNA干扰也因此而停止进行[18]。
体外恶性转化
![](http://images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/8/85/HEK_293_cells_grown_in_tissue_culture_medium.jpg/220px-HEK_293_cells_grown_in_tissue_culture_medium.jpg)
细胞生物学研究者为了方便研究,可能会在体外(in vitro)使用病毒感染等方法对动物细胞进行恶性转化,获得永生化细胞系。比如HEK 293细胞就是使用5型腺病毒DNA片段恶性转化的人胚肾细胞。另外,在体外进行恶性转化对研究体内(in vivo)的恶性转化过程也有一定助益[19][3][20]。
参见
参考文献
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- ^ 2.0 2.1 Tsz-Kwong Man; et al. Chapter 15 – Genomic and Proteomic Profiling of Osteosarcoma. Bone Cancer: Progression and Therapeutic Approaches. 2010: 181–192.
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- ^ 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.
- ^ 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.
- ^ 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
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- ^ 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)
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