BCL-2, BAX, BCL-X(L), AND BCL-X(S) EXPRESSION IN NORMAL AND NEOPLASTIC OVARIAN TISSUES

The bcl-2 family of proteins includes some important regulators of apo ptosis, Among these, bcl-2 and bcl-x(L) prevent cells from entering ap optosis, whereas bar and bcl-x(S) can induce cell death, Alterations i n the control of this process can lead to a decrease in cell death, th us contributing to neoplastic growth, Diminished susceptibility to che motherapy has also been attributed, in in vitro systems, to alteration s in the levels of bcl-2, bar, or bcl-x, We analyzed the expression of bcl-2, bar, bcl-x(L), and bcl-x(S) in normal and neoplastic ovarian t issues by reverse transcriptase-PCR and Western blotting, The RNA and protein levels were significantly correlated for all genes, Interestin gly, the levels of these genes in normal and neoplastic tissues were s ignificantly different: bcl-2 was higher in normal tissue (P < 0.002), whereas bar and bcl-x(L) were higher in carcinoma (P < 0.018 and P < 0.030, respectively), bcl-x(S) was present at low levels in 83% of neo plastic samples and was undetectable in normal tissue, Reverse transcr iptase-PCR analysis of 74 tumors showed no major correlation with clin icopathological parameters or with response to chemotherapy, Only bar and bcl-x(L) were correlated with progesterone receptor levels (n = 29 , r = +0.44, P < 0.0189, and r = -0.40, P < 0.035, respectively), No c orrelation was found with estrogen receptor levels or with p53 immunos taining, Our data indicate that the regulation of the bcl-2 family of proteins differs between normal and neoplastic ovarian tissues, Moreov er, the modulation of these genes in ovarian carcinoma is different co mpared to other tissues; therefore, tissue specificity is very importa nt in regulation of the bcl-2 family of proteins.