title: Mammogenic hormones differentially modulate keratinocyte growth factor (KGF)-induced proliferation and KGF receptor expression in cultured mouse mammary gland epithelium.
abstract: Stromally derived keratinocyte growth factor (KGF) can play an important role in mammary gland development as a mesenchymal/stromal mediator of epithelial growth and morphogenesis. However, the possible coordinate regulation of mammary gland development by mammogenic hormones and KGF is unexplored. In these studies, the direct effect of mammogenic hormones on KGF-mediated mammary epithelial mitogenesis and expression of the KGF receptor was examined using primary mouse mammary epithelium growing in serum-free, collagen gel cell culture. Addition of KGF produced an average 7-fold increase in cell number after 10 days of culture. This effect of KGF was further increased in the presence of PRL (9-fold) or progesterone (P; 15-fold), with the combination of P and PRL (22-fold) producing the strongest synergistic stimulation. Estrogen did not show any additional stimulation of growth either alone or in combination with PRL and/or P. Ribonuclease protection analysis showed that epithelial cells grown in medium supplemented with P, but not PRL or estrogen, exhibited a 10-fold higher steady state level of KGF receptor (KGFR) messenger RNA (mRNA). KGFR expression was not induced by short term P exposure, suggesting an effect on mRNA stability rather than transcriptional activation. Time-course studies showed that an early decrease in the level of KGFR mRNA in basal cultures was significantly reduced by P addition. Measurement of RNA turnover after actinomycin D treatment showed that P increased the t(1/2) of KGFR mRNA compared with basal medium. Thus, P and PRL may differentially potentiate the direct mitogenic effect of KGF: P partly by elevation of the level of KGFR mRNA, and PRL principally by intracellular pathways not affecting KGFR expression.
authors.affiliation: Kansas Cancer Institute, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160-7810, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Pedchenko
authors.forename: W T
authors.initials: WT
authors.lastname: Imagawa
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D015870:Gene Expression / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor / Q000235:genetics*
chemical_list: C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D006728:Hormones; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D051523:Fibroblast Growth Factor 7; D011374:Progesterone; D004958:Estradiol; D005346:Fibroblast Growth Factors; D011388:Prolactin; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor