Choo C K, Rorke E A, Eckert R L
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970.
J Gen Virol. 1994 May;75 ( Pt 5):1139-47. doi: 10.1099/0022-1317-75-5-1139.
CaSki cells are a human papillomavirus type 16 (HPV-16)-positive cell line that serves as a model for the study of advanced cervical carcinoma. Calcium is an important regulator of normal ectocervical epithelial cell differentiation. HPV E6 and E7 gene products are thought to be important in the process of cervical cell immortalization and hence important in the development of cervical cancer. In the present study we examine the relationship between CaSki cell differentiation and expression of the papillomavirus oncogenes. Shifting CaSki cells from medium containing low (0.06 mM) to high (1.4 mM) calcium results in an increase in cell-cell contact and increased differentiation as measured by an increase in the level of mRNA encoding cytokeratin K13, involucrin and type 1 transglutaminase, which are markers of differentiation in the cervical epithelium. In contrast, E6/E7 transcripts are produced in a differentiation-independent constitutive manner. These results and those from our previous experiments with HPV-16-immortalized but non-tumorigenic cell lines suggest that the constitutive, differentiation-independent expression of E6/E7 levels is a property of both tumorigenic and non-tumorigenic HPV-16-positive cancer cells.
CaSki细胞是一种人乳头瘤病毒16型(HPV - 16)阳性细胞系,可作为研究晚期宫颈癌的模型。钙是正常宫颈外膜上皮细胞分化的重要调节因子。HPV E6和E7基因产物被认为在宫颈细胞永生化过程中起重要作用,因此在宫颈癌的发展中也很重要。在本研究中,我们检测了CaSki细胞分化与乳头瘤病毒癌基因表达之间的关系。将CaSki细胞从含有低钙(0.06 mM)的培养基转移到高钙(1.4 mM)培养基中,会导致细胞间接触增加,分化增强,这可通过编码细胞角蛋白K13、外皮蛋白和1型转谷氨酰胺酶的mRNA水平升高来衡量,这些都是宫颈上皮分化的标志物。相反,E6/E7转录本以与分化无关的组成性方式产生。这些结果以及我们之前对HPV - 16永生化但无致瘤性的细胞系的实验结果表明,E6/E7水平的组成性、与分化无关的表达是致瘤性和非致瘤性HPV - 16阳性癌细胞的共同特性。