A bcl-xS adenovirus selectively induces apoptosis in transformed cells compared to normal mammary cells

Oncogenes which drive the cell cycle, such as c-myc, can sensitize cells to apoptosis. This suggests the possibility that the expression of genes such as bcl-2 or bcl-xL is required to inhibit apoptosis induced by oncogene ex pression. We hypothesized that inhibition of Bcl-2/Bcl-xL by the pro-apopto tic Bcl-xS protein, would result in selective induction of apoptosis in mam mary carcinoma cells compared to their nontransformed counterparts. Therefo re, we compared the effects of Bcl-xS expression delivered by a bcl-xS aden ovirus (bcl-xS-Adv) vector, on viability and apoptosis of nontransformed ve rsus transformed mammary epithelial cells. We report that c-myc-transformed murine mammary cells are extremely sensitive to apoptosis induced by the b cl-xS adenovirus (bcl-xS-Adv) vector, whereas immortalized, nontransformed murine mammary cells are relatively resistant to apoptosis induced by this vector. Likewise, human mammary epithelial cells transduced with c-erbB-2 w ere more sensitive to apoptosis induced by the bcl-xS vector than the nontr ansformed parental cells, Similar results were obtained when we tested the effects of bcl-xS adenoviral infection on primary normal human mammary epit helial cells and SUM-190 PT cells, (a c-erbB-2 over-expressing human mammar y carcinoma cell line) grown on Matrigel. These data are consistent with th e hypothesis that inhibition of Bcl-2/Bcl-xL can result in selective killin g of cancer cells compared to their nontransformed counterparts.