Abstract
Androgen ablation is the primary treatment modality for patients with metastatic prostate cancer; however, the role of androgen receptor signaling in prostate cancer development remains enigmatic. Using a series of genetically defined immortalized and tumorigenic human prostate epithelial cells, we found that introduction of the androgen receptor induced differentiation of transformed prostate epithelial cells to a luminal phenotype reminiscent of organ-confined prostate cancer when placed in the prostate microenvironment. Moreover, androgen receptor expression converted previously androgen-independent, tumorigenic prostate epithelial cells into cells dependent on testosterone for tumor formation. These observations indicate that androgen receptor expression is oncogenic and addictive for the human prostate epithelium.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Androgens / metabolism
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Androgens / physiology*
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / physiology
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology*
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DNA-Binding Proteins
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Epithelial Cells / physiology
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Gene Expression Profiling
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Genes, ras / genetics
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Humans
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Male
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Mice
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Multigene Family
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Prostate / metabolism
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Prostate / pathology*
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Prostate / physiology
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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Receptors, Androgen / biosynthesis
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Receptors, Androgen / genetics
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Receptors, Androgen / physiology*
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Telomerase / genetics
Substances
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Androgens
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DNA-Binding Proteins
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Receptors, Androgen
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Telomerase