PMID- 16301332 OWN - NLM STAT- MEDLINE DCOM- 20060106 LR - 20181113 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 171 IP - 4 DP - 2005 Nov 21 TI - Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model. PG - 663-73 AB - Members of the fibroblast growth factor (FGF) family and the FGF receptors (FGFRs) have been implicated in mediating various aspects of mammary gland development and transformation. To elucidate the molecular mechanisms of FGFR1 action in a context that mimics polarized epithelial cells, we have developed an in vitro three-dimensional HC11 mouse mammary epithelial cell culture model expressing a drug-inducible FGFR1 (iFGFR1). Using this conditional model, iFGFR1 activation in these growth-arrested and polarized mammary acini initially led to reinitiation of cell proliferation, increased survival of luminal cells, and loss of cell polarity, resulting in the disruption of acinar structures characterized by the absence of an empty lumen. iFGFR1 activation also resulted in a gain of invasive properties and the induction of matrix metalloproteinase 3 (MMP-3), causing the cleavage of E-cadherin and increased expression of smooth muscle actin and vimentin. The addition of a pan MMP inhibitor abolished these phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or survival. FAU - Xian, Wa AU - Xian W AD - Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. FAU - Schwertfeger, Kathryn L AU - Schwertfeger KL FAU - Vargo-Gogola, Tracy AU - Vargo-Gogola T FAU - Rosen, Jeffrey M AU - Rosen JM LA - eng GR - R37 CA016303/CA/NCI NIH HHS/United States GR - CA 97676-01/CA/NCI NIH HHS/United States GR - R01 CA016303/CA/NCI NIH HHS/United States GR - CA16303/CA/NCI NIH HHS/United States GR - F32 CA097676/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Cadherins) RN - 0 (RNA, Small Interfering) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Apoptosis MH - Basement Membrane/metabolism MH - Cadherins/metabolism MH - Cell Line MH - Cell Movement MH - Cell Proliferation MH - Cell Survival MH - Dimerization MH - Epithelial Cells/*cytology MH - Epithelium/metabolism MH - Fluorescent Antibody Technique, Indirect MH - Imaging, Three-Dimensional MH - Immunoblotting MH - Mammary Glands, Animal/*cytology MH - Matrix Metalloproteinase 3/biosynthesis/metabolism MH - Mesoderm/metabolism MH - Mice MH - Microscopy, Confocal MH - Models, Biological MH - Phenotype MH - Plasmids/metabolism MH - RNA, Small Interfering/metabolism MH - Receptor, Fibroblast Growth Factor, Type 1/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Time Factors MH - Wound Healing PMC - PMC2171554 EDAT- 2005/11/23 09:00 MHDA- 2006/01/07 09:00 PMCR- 2006/05/21 CRDT- 2005/11/23 09:00 PHST- 2005/11/23 09:00 [pubmed] PHST- 2006/01/07 09:00 [medline] PHST- 2005/11/23 09:00 [entrez] PHST- 2006/05/21 00:00 [pmc-release] AID - jcb.200505098 [pii] AID - 200505098 [pii] AID - 10.1083/jcb.200505098 [doi] PST - ppublish SO - J Cell Biol. 2005 Nov 21;171(4):663-73. doi: 10.1083/jcb.200505098.