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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.
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January 1993,
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January 1997,
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R T Altstock, and
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January 2005,
Cell research,
D Ronen, and
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G F Vande Woude, and
I Tsarfaty
January 1994,
Verhandlungen der Deutschen Gesellschaft fur Pathologie,
D Ronen, and
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I Tsarfaty
September 2006,
Cancer research,
D Ronen, and
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L Mittelman, and
T Sobe, and
J H Resau, and
G F Vande Woude, and
I Tsarfaty
January 1993,
EXS,
D Ronen, and
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M Firon, and
L Mittelman, and
T Sobe, and
J H Resau, and
G F Vande Woude, and
I Tsarfaty
March 2015,
Aging,
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R T Altstock, and
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G F Vande Woude, and
I Tsarfaty
January 1993,
Symposia of the Society for Experimental Biology,
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G F Vande Woude, and
I Tsarfaty
February 2000,
Breast cancer research and treatment,
D Ronen, and
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M Firon, and
L Mittelman, and
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Molecular cancer therapeutics,
