EXPRESSION OF CELLULAR GENES IN HPV16-IMMORTALIZED AND CIGARETTE-SMOKE CONDENSATE-TRANSFORMED HUMAN ENDOCERVICAL CELLS

We studied the molecular mechanism of successive multistep cervical ca rcinogenic progression with our previously established in vitro model system. This system vias composed of primary human endocervical cells (HEN), two lines of HEN immortalized by HPV16 and their counterparts s ubsequently malignantly transformed by cigarette smoke condensate (CSC ). The expression was examined of diverse cellular genes associated wi th oncogenesis and senescence, especially for cervical cancer. Consist ent results were seen for the pairs of immortalized and malignantly tr ansformed lines. Immortalization of HEN by HPV16 resulted in enhanced expression of H-ras, c-myc, B-myb, p53, p16(INK4) and PCNA mRNA; enhan ced expression of p16 and PCNA proteins; decreased expression of WAF1/ p21/Cip1/Sid1 and fibronectin mRNA; and decreased p53 protein. On the other hand, the CSC-transformed counterparts of HPV16-immortalized cel ls had up-regulated levels of B-myb, p53 and WAF1 mRNA and p53 protein . Our results indicate that the differential activation or inactivatio n of multiple cellular genes is important for the immortalization, as well as the transformation, of human cervical cells. Further, we sugge st that our in vitro model system is useful for investigating the mole cular mechanism of multistep cervical carcinogenesis. (C) 1997 Wiley-L iss, Inc.