Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / toxicity*
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Apoptosis / drug effects*
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Breast Neoplasms
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Cell Division / drug effects
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Cell Line
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Enzyme-Linked Immunosorbent Assay
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Humans
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Kanamycin Kinase
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Oncogene Proteins, Viral / metabolism
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Paclitaxel / toxicity*
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Papillomaviridae / genetics
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Papillomaviridae / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / biosynthesis
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins c-bcl-2*
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Recombinant Proteins / biosynthesis
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Repressor Proteins*
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Transfection
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Tumor Cells, Cultured
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bcl-X Protein
Substances
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Antineoplastic Agents
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BCL2L1 protein, human
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E6 protein, Human papillomavirus type 16
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Oncogene Proteins, Viral
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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Repressor Proteins
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bcl-X Protein
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Phosphotransferases (Alcohol Group Acceptor)
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Kanamycin Kinase
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Paclitaxel