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pubmed-article:7518821pubmed:abstractTextInsulin-like growth factors (IGFs) are important regulators of epithelial cell growth. The mitogenic activity of these factors is influenced by the levels of extracellular IGF binding proteins, including insulin-like growth factor binding protein 3 (IGFBP-3). In the present report we study the effects of epidermal growth factor (EGF) and all-trans-retinoic acid (RA) on IGFBP-3 RNA and protein levels in human papillomavirus-immortalized cervical epithelial cells. Treatment of ECE16-1 cells with 3-20 ng/ml EGF causes a marked reduction in IGFBP-3 levels. In contrast, 1 microM RA increases IGFBP-3 mRNA and protein levels in the presence or absence of 20 ng/ml EGF. The response is concentration dependent with a half-maximal increase observed at 1 nM RA. RA is able to reverse the EGF suppression when added simultaneously or 3 days after initiation of EGF treatment. Conversely, when cells are treated with RA, IGFBP-3 levels increase within 24 h and subsequent addition of EGF is without effect. Thus, the RA-dependent increase in IGFBP-3 levels is dominant over the EGF suppression. The increased IGFBP-3 levels are correlated with RA suppression of proliferation. Similar RA effects on IGFBP-3 mRNA levels were observed in other cervical epithelial cell lines (i.e., ECE16-D1, ECE16-D2, and CaSki). These results suggest that RA may act to inhibit cervical cell growth by increasing IGFBP-3 levels and reducing the extracellular concentration of free insulin-like growth factor I (IGFI) and/or alternatively, IGFBP-3 may inhibit cell growth by direct effects on the cell, independent of IGFI.lld:pubmed
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pubmed-article:7518821pubmed:authorpubmed-author:EckertR LRLlld:pubmed
pubmed-article:7518821pubmed:authorpubmed-author:HembreeJ RJRlld:pubmed
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pubmed-article:7518821pubmed:pagination265-74lld:pubmed
pubmed-article:7518821pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:7518821pubmed:articleTitleRegulation of insulin-like growth factor 1 binding protein 3 levels by epidermal growth factor and retinoic acid in cervical epithelial cells.lld:pubmed
pubmed-article:7518821pubmed:affiliationDepartment of Physiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4970.lld:pubmed
pubmed-article:7518821pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:7518821pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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