Bcl-2 protooncogene expression in cervical carcinoma cell lines containing inactive p53.
Bcl-2 protein expression has been found to block apoptosis and its overexpression has been implicated in lymphoid malignancies where the chromosomal translocation t(14;18) is present. In this study we investigated bcl-2 transcription and protein expression in cultured cervical carcinoma cell lines and keratinocytes. Western blotting and immunofluorescence 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 chromosomal translocation or rearrangement at the major breakpoint-cluster region (MBR) of the bcl-2 gene using either Southern blot or polymerase chain reaction (PCR) analyses. Northern blot analysis demonstrated low levels of bcl-2 transcription in HeLa, CaSki, and C-33A cell lines while reverse transcriptase (RT)-PCR demonstrated bcl-2 transcription in all cervical carcinoma cell lines which had bcl-2 protein expression. Thus, these data suggest that bcl-2 expression occurs in cervical carcinoma cell lines in the absence of chromosomal translocation or rearrangement of the bcl-2 gene. However, each of these cervical carcinoma cell lines contains inactive p53, either due to mutation (C-33A and HT-3) or via complexation and degradation with human papillomavirus (HPV) 16/18 E6 protein (HeLa and CaSki). Thus, functional p53, which can induce apoptosis in certain cells, is not present in these cervical cells which have increased bcl-2 expression. Increased bcl-2 expression under conditions of p53 inactivation may provide cells with a selective advantage for survival and consequently play a role in the development of cervical carcinogenesis.
Liang
X H
XH
Laboratory for Cell Biology, School of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Mungal
S
S
Ayscue
A
A
Meissner
J D
JD
Wodnicki
P
P
Hockenbery
D
D
Lockett
S
S
Herman
B
B
D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016158:Genes, p53; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry*
D014764:Viral Proteins