IGF-binding proteins in human prostate tumor cells: expression and regulation by 1,25-dihydroxyvitamin D3.
The expression of the six known insulin-like growth factor binding proteins (IGFBPs) and their corresponding messenger RNAs has been examined in three cell lines established from surgical and biopsy specimens of human prostate carcinoma. All three cell lines produced both IGFBP-4 and IGFBP-6 and the respective mRNAs; expression of IGFBP-6 has not been previously demonstrated in human prostate tumor cells. No other binding proteins were detected. The levels of IGFBP mRNAs were not regulated by androgens or IGF-1, but the level of IGFBP-6 mRNA was sharply increased by 1,25-dihydroxyvitamin D3 (1,25(OH)D3). The stimulation was dose-dependent with a maximum effect at 10 nM 1,25(OH)D3 and a clearly discernible effect at 0.1 nM. The results support a role for vitamin D in the control of prostate tumor growth, mediated at least in part by interaction with IGFs and specific IGFBPs.
Drivdahl
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Research Service, Department of Veterans Affairs Medical Center, Tacoma, Washington 98493.
Loop
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Andress
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Ostenson
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D001706:Biopsy; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D002117:Calcitriol / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol