Met-HGF/SF mediates growth arrest and differentiation in T47D breast cancer cells

Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent growth fa ctor that exerts mitogenic, motogenic, and morphogenic effects. To elucidat e the cellular mechanisms underlying the pluripotent function of this growt h factor, T47D human breast cancer cells were transfected with human hgf/sf . The hgf/sf-positive clones exhibited different levels of biologically fun ctional HGF/SF expression and up-regulation of endogenous Met (HGF/SF recep tor) expression. In addition, a constitutive phosphorylation of the recepto r on tyrosine residues was detected, establishing a Met-HGF/SF autocrine lo op. The autocrine activation of Met caused marked inhibition in cell growth accompanied by cell accumulation at G(0)/G(1). These cells underwent termi nal 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 si gnal transduction pathway, is capable of inducing growth arrest and differe ntiation in certain breast cancer cells and, thus, may have potential as th erapeutic and/or prognostic tools in breast cancer treatment.