Abstract
Comparison of LCC2, the E(2)-independent, tamoxifen-resistant subline of the MCF-7 human breast cancer cell line with its parent line, disclosed that it is more resistant to growth inhibition and apoptosis induction by a variety of agents acting by diverse mechanisms. Thus, LCC2 cells can serve as a useful in-vitro model for the study of the molecular mechanisms of this resistance. It was found that bcl-2 protein and mRNA were elevated and that bax protein and mRNA were reduced in LCC2 compared with MCF-7 cells. Incubation of both lines in the presence of bcl-2 antisense caused growth inhibition and reduced bcl-2 protein levels only in MCF-7 cells, suggesting the involvement of bcl-2 in the regulation of normal growth of breast cancer cells. Increased bcl-2 expression in breast cancer cells may correlate with their resistance to growth inhibitory agents. Bcl-2 is a useful target for enhancing the effects of growth inhibitory agents.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Drug Resistance, Neoplasm
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Estradiol / pharmacology*
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Estradiol / physiology
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Estrogen Receptor Modulators / pharmacology
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Growth Inhibitors / pharmacology*
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Humans
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Neoplasms, Hormone-Dependent / drug therapy
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Neoplasms, Hormone-Dependent / metabolism*
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Neoplasms, Hormone-Dependent / pathology
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Oligonucleotides, Antisense / genetics
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Oligonucleotides, Antisense / pharmacology
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Messenger / biosynthesis
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Tamoxifen / pharmacology
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Tumor Cells, Cultured
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bcl-2-Associated X Protein
Substances
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Antineoplastic Agents
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BAX protein, human
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Estrogen Receptor Modulators
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Growth Inhibitors
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Oligonucleotides, Antisense
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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bcl-2-Associated X Protein
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Tamoxifen
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Estradiol