Park D J, Wilczynski S P, Paquette R L, Miller C W, Koeffler H P
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.
Oncogene. 1994 Jan;9(1):205-10.
Human papillomavirus (HPV) infection has been strongly linked to the development of cervical carcinoma. Two viral oncoproteins, E6 and E7, produced by HPV, have been shown to immortalize primary human genital epithelial cells by interacting with the protein products of cellular tumor suppressor genes p53 and Rb, respectively. E6 binds to the cellular p53 protein promoting p53 degradation and inactivity. This mechanism has been suggested to contribute to the oncogenesis of HPV-positive anogenital cancers. In HPV-negative cervical carcinoma, p53 mutation is thought to be the possible mechanism of oncogenesis. We have studied 257 cervical carcinoma specimens for HPV infection by Southern blot analysis and polymerase chain reaction (PCR). Of 257 samples, 39 were HPV-negative. We have further studied 21 HPV-negative specimens for p53 mutations utilizing PCR amplification of genomic DNA followed by single-stranded conformation polymorphism (SSCP) analysis and DNA sequencing. We found only two missense point mutations of p53 gene. In summary, although inactivation of p53 mediated either by E6 or by mutations may be an important key step in the development of cervical carcinoma, our study suggests that other mechanisms may also be involved in development of cervical cancer.
人乳头瘤病毒（HPV）感染与宫颈癌的发生密切相关。HPV产生的两种病毒癌蛋白E6和E7，已被证明分别通过与细胞肿瘤抑制基因p53和Rb的蛋白质产物相互作用，使原代人泌尿生殖上皮细胞永生化。E6与细胞p53蛋白结合，促进p53降解并使其失活。有人认为这种机制有助于HPV阳性肛门生殖器癌的肿瘤发生。在HPV阴性的宫颈癌中，p53突变被认为是可能的肿瘤发生机制。我们通过Southern印迹分析和聚合酶链反应（PCR）研究了257例宫颈癌标本中的HPV感染情况。在257个样本中，39个为HPV阴性。我们利用基因组DNA的PCR扩增，随后进行单链构象多态性（SSCP）分析和DNA测序，对21个HPV阴性标本进一步研究了p53突变情况。我们仅发现了p53基因的两个错义点突变。总之，尽管由E6介导或由突变介导的p53失活可能是宫颈癌发生过程中的一个重要关键步骤，但我们的研究表明，其他机制也可能参与宫颈癌的发生。
