Inhibition of growth and cell cycle arrest of ARCaP human prostate cancer cells by ectopic expression of ER-alpha.
The estrogen receptor-alpha (ER-alpha) is a ligand-dependent transcription factor that regulates the growth, differentiation, and development of hormone-responsive target organs. While ER-alpha has been reported to play critical role in the pathogenesis and prognosis of breast and prostate cancers, its possible functional role in regulating prostate cancer cell growth in a ligand-dependent or -independent manner is poorly understood. We addressed this question by stably transfecting wild type (wt) ER-alpha cDNA into an invasive estrogen receptor-negative human prostate cancer cell line ARCaP. We isolated several clonal lines of transfected cells expressing varying levels of ER-alpha. The ectopic expression of wt ER-a markedly inhibited the growth of ARCaP cells in vitro in an ER-a dose-dependent but ligand-independent manner. Flow cytometric analysis of the wt ER-alpha-transfected ARCaP cells revealed that wt ER-alpha expression arrested cell growth in G1 phase. Our results suggest that ER-alpha may regulate prostate cell growth and participate in the pathogenesis of prostate cancer. ER-alpha may be delivered and expressed ectopically to target prostate cancer progression.
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Department of Urology, University of Virginia School of Medicine, Charlottesville 22908, USA. QY3X@Virginia.edu
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Edlund
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Chung
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Zhau
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D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011960:Receptors, Estrogen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen