Abstract
The growth of isolated epithelial and stromal cells from both androgen-dependent normal rat prostate and an androgen-responsive model rat prostate tumor is androgen-independent. When added to co-cultures of epithelial and stromal cells separated by a semipermeable membrane, androgen stimulated epithelial cell growth without an effect on stromal cell growth. Northern blot and nuclease protection analysis of mRNA revealed that stromal cells specifically expressed an androgen-sensitive secreted member of the heparin-binding fibroblast growth factor family [keratinocyte growth factor (KGF)/fibroblast growth factor-7]. KGF was mitogenic for epithelial cells, but not for stromal cells. Epithelial cells expressed specifically a splice variant of the bek receptor gene that specifically binds KGF. Expression of the bek receptor gene in stromal cells was undetectable by Northern blot and nuclease protection analyses. The results suggest that stromal cell-derived KGF has the properties of an andromedin, which mediates the indirect control of epithelial cell proliferation by androgen through a directional stromal-to-epithelial cell paracrine mechanism.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Division / drug effects
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Cells, Cultured
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Connective Tissue / physiology*
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Connective Tissue Cells
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Dihydrotestosterone / pharmacology*
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Epithelial Cells
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Epithelium / drug effects
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Fibroblast Growth Factor 10
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Fibroblast Growth Factor 7
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Fibroblast Growth Factors*
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Fibroblasts / drug effects
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Fibroblasts / metabolism*
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Gene Expression Regulation / drug effects
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Growth Substances / biosynthesis
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Growth Substances / genetics
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Growth Substances / physiology*
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Male
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Molecular Sequence Data
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Prostate / cytology
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Prostate / metabolism*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Protein-Tyrosine Kinases / biosynthesis
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Rats
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Receptor Protein-Tyrosine Kinases*
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Receptor, Fibroblast Growth Factor, Type 2
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Receptors, Fibroblast Growth Factor / biosynthesis
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Testosterone / pharmacology*
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Tumor Cells, Cultured
Substances
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Fgf7 protein, rat
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Fibroblast Growth Factor 10
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Growth Substances
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Receptors, Fibroblast Growth Factor
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Dihydrotestosterone
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Fibroblast Growth Factor 7
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Testosterone
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Fibroblast Growth Factors
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Fgfr2 protein, rat
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 2