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 expression. We hypothesized that inhibition of Bcl-2/Bcl-xL by the pro-apoptotic Bcl-xS protein, would result in selective induction of apoptosis in mammary carcinoma cells compared to their nontransformed counterparts. Therefore, we compared the effects of Bcl-xS expression delivered by a bcl-xS adenovirus (bcl-xS-Adv) vector, on viability and apoptosis of nontransformed versus transformed mammary epithelial cells. We report that c-myc-transformed murine mammary cells are extremely sensitive to apoptosis induced by the bcl-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 were more sensitive to apoptosis induced by the bcl-xS vector than the nontransformed parental cells. Similar results were obtained when we tested the effects of bcl-xS adenoviral infection on primary normal human mammary epithelial cells and SUM-190 PT cells, (a c-erbB-2 over-expressing human mammary carcinoma cell line) grown on Matrigel. These data are consistent with the hypothesis that inhibition of Bcl-2/Bcl-xL can result in selective killing of cancer cells compared to their nontransformed counterparts.
Sumantran
V N
VN
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109-0942, USA.
Lee
D S
DS
Woods Ignatoski
K M
KM
Ethier
S P
SP
Wicha
M S
MS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005472:Fluorouracil / Q000494:pharmacology; D016259:Genes, myc; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology*; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D051020:bcl-X Protein
D005472:Fluorouracil; D017239:Paclitaxel; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D051020:bcl-X Protein; C494811:BCL2L1 protein, human