PMID- 10074906 OWN - NLM STAT- MEDLINE DCOM- 19990521 LR - 20131121 IS - 1044-9523 (Print) IS - 1044-9523 (Linking) VI - 10 IP - 2 DP - 1999 Feb TI - Met-HGF/SF mediates growth arrest and differentiation in T47D breast cancer cells. PG - 131-40 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent growth factor that exerts mitogenic, motogenic, and morphogenic effects. To elucidate the cellular mechanisms underlying the pluripotent function of this growth factor, T47D human breast cancer cells were transfected with human hgf/sf. The hgf/sf-positive clones exhibited different levels of biologically functional HGF/SF expression and up-regulation of endogenous Met (HGF/SF receptor) expression. In addition, a constitutive phosphorylation of the receptor on tyrosine residues was detected, establishing a Met-HGF/SF autocrine loop. The autocrine activation of Met caused marked inhibition in cell growth accompanied by cell accumulation at G0/G1. These cells underwent terminal cell differentiation as determined by morphological changes, synthesis of milk proteins such as beta-casein and alpha-lactalbumin, and production of lipid vesicles. Our results demonstrate that Met-HGF/SF, an oncogenic signal transduction pathway, is capable of inducing growth arrest and differentiation in certain breast cancer cells and, thus, may have potential as therapeutic and/or prognostic tools in breast cancer treatment. FAU - Ronen, D AU - Ronen D AD - Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Israel. FAU - Altstock, R T AU - Altstock RT FAU - Firon, M AU - Firon M FAU - Mittelman, L AU - Mittelman L FAU - Sobe, T AU - Sobe T FAU - Resau, J H AU - Resau JH FAU - Vande Woude, G F AU - Vande Woude GF FAU - Tsarfaty, I AU - Tsarfaty I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Cell Growth Differ JT - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JID - 9100024 RN - 0 (Caseins) RN - 42HK56048U (Tyrosine) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9007-49-2 (DNA) RN - 9013-90-5 (Lactalbumin) RN - AE28F7PNPL (Methionine) SB - IM MH - Blotting, Western MH - Breast Neoplasms/*pathology MH - Caseins/metabolism MH - Cell Cycle/physiology MH - Cell Differentiation MH - Cell Division MH - DNA/metabolism MH - Flow Cytometry MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lactalbumin/metabolism MH - Methionine/metabolism MH - Microscopy, Fluorescence MH - Phenotype MH - Signal Transduction MH - Time Factors MH - Transfection MH - Tumor Cells, Cultured MH - Tyrosine/metabolism MH - Up-Regulation EDAT- 1999/03/13 00:00 MHDA- 1999/03/13 00:01 CRDT- 1999/03/13 00:00 PHST- 1999/03/13 00:00 [pubmed] PHST- 1999/03/13 00:01 [medline] PHST- 1999/03/13 00:00 [entrez] PST - ppublish SO - Cell Growth Differ. 1999 Feb;10(2):131-40.