Overexpression of Bcl-XS sensitizes MCF-7 cells to chemotherapy-induced apoptosis.
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. We used Bcl-XS, a dominant negative inhibitor of Bcl-2 and Bcl-XL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Bcl-XS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. Using an ELISA assay which quantitates DNA damage, we demonstrate that this sensitization is due to apoptosis, suggesting the therapeutic utility of targeting this pathway.
Sumantran
V N
VN
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0724, USA.
Ealovega
M W
MW
Nuñez
G
G
Clarke
M F
MF
Wicha
M S
MS
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019868:Kanamycin Kinase; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D017239:Paclitaxel / Q000633:toxicity*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000096:biosynthesis; D012097:Repressor Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051020:bcl-X Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase; D017239:Paclitaxel