BCL-2 PROTOONCOGENE EXPRESSION IN CERVICAL-CARCINOMA CELL-LINES CONTAINING INACTIVE P53

Bcl-2 protein expression has been found to block apoptosis and its ove rexpression has been implicated in lymphoid malignancies where the chr omosomal translocation t(14;18) is present. In this study we investiga ted bcl-2 transcription and protein expression in cultured cervical ca rcinoma cell lines and keratinocytes. Western blotting and immunofluor escence microscopy demonstrated bcl-2 expression in the cytoplasm of 4 out of 5 cervical carcinoma cell lines examined (HeLa, CaSki, C-33A, and HT-3, but not SiHa). Bcl-2 protein expression was undetectable in normal keratinocytes. None of the cell lines examined demonstrated chr omosomal translocation or rearrangement at the major breakpoint-cluste r region (MBR) of the bcl-2 gene using either Southern blot or polymer ase chain reaction (PCR) analyses. Northern blot analysis demonstrated low levels of bcl-2 transcription in HeLa, CaSki, and C-33A cell line s while reverse transcriptase (RT)-PCR demonstrated bcl-2 transcriptio n in all cervical carcinoma cell lines which had bcl-2 protein express ion. Thus, these data suggest that bcl-2 expression occurs in cervical carcinoma cell lines in the absence of chromosomal translocation or r earrangement of the bcl-2 gene. However, each of these cervical carcin oma cell lines contains inactive p53, either due to mutation (C-33A an d HT-3) or via complexation and degradation with human papillomavirus (HPV) 16/18 E6 protein (HeLa and CaSki). Thus, functional p53, which c an induce apoptosis in certain cells, is not present in these cervical cells which have increased bcl-2 expression. Increased bcl-2 expressi on under conditions of p53 inactivation may provide cells with a selec tive advantage for survival and consequently play a role in the develo pment of cervical carcinogenesis. (C) 1995 Wiley-Liss, Inc.