MODULATION OF PROLIFERATION AND TUMORIGENIC POTENTIAL OF CERVICAL-CARCINOMA CELLS BY THE EXPRESSION OF SENSE AND ANTISENSE P53

Previous studies from our laboratory demonstrated that overexpression of wild-type p53 suppresses the growth and alters the differentiation pattern of HPV-immortalized keratinocytes (Woodworth et al: Cell Growth Differ 4: 367-376, 1993). In the present report we describe the use of sense and antisense p53 retroviral vectors to modulate the expression levels of the p53 tumor suppressor gene in cervical carcinoma cells. Representative cell lines (C-4 I, ME-180 and C-33 A) were selected for this study on the basis of their various expression levels of either wild-type or mutated p53, and also of their content of integrated human papillomavirus sequences. Our results show that p53 overexpression from the sense construct decreased the growth rate and tumorigenic potential of the HPV-negative C-4 I cell line, whereas it had no effect on the HPV-positive ME-180 and C-33 A cells. However, examination of the individual colonies early after transfection with sense constructs by light microscopy showed that overexpression of wild-type p53 in ME-180 induced significant morphological alterations resulting in cellular senescence. Nevertheless, the p53 overexpressing, ME-180-derived cell line established after selection did not exhibit any major changes compared to the parental cell line. In the case of C-33 A, the presence of high levels of mutant p53 prevented the exogenous wild-type p53 from causing any significant modulatory action on their proliferation or neoplastic phenotype.