Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, México DF, Mexico.
Virology. 2012 Nov 25;433(2):337-45. doi: 10.1016/j.virol.2012.08.024. Epub 2012 Sep 11.
HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin.
HPV16 E7 癌蛋白在 K14E7 转基因小鼠中的表达，在经过 6 个月的协同致癌剂 17β-雌二醇治疗后，会引发宫颈癌。在未治疗的小鼠中，E7 也会在生命后期引发皮肤肿瘤，尽管其发生率较低。这些发现表明，E7 改变了宫颈和皮肤细胞的功能，从而使这些器官容易发生肿瘤形成。我们使用微阵列技术，确定了未经雌激素治疗的年轻成年 K14E7 转基因小鼠宫颈和皮肤组织中的全局基因表达谱。在这些组织中，E7 癌蛋白改变了参与包括信号转导、运输、代谢过程、细胞黏附、细胞凋亡、细胞分化、免疫反应和炎症反应在内的多个生物学过程的基因的转录模式。在 E7 失调的基因中，包括以前未知与宫颈癌有关的基因，如宫颈中的 DMBT1、GLI1 和 17βHSD2，以及皮肤中的 MMP2、12、14、19 和 27。
