Ronen D, Altstock R T, Firon M, Mittelman L, Sobe T, Resau J H, Vande Woude G F, Tsarfaty I
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Israel.
Cell Growth Differ. 1999 Feb;10(2):131-40.
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.
肝细胞生长因子/分散因子（HGF/SF）是一种具有多能性的生长因子，可发挥促有丝分裂、促运动和促形态发生作用。为阐明这种生长因子多能性功能的细胞机制，用人类hgf/sf转染了T47D人乳腺癌细胞。hgf/sf阳性克隆表现出不同水平的具有生物学功能的HGF/SF表达以及内源性Met（HGF/SF受体）表达上调。此外，检测到受体酪氨酸残基的组成性磷酸化，从而建立了Met-HGF/SF自分泌环。Met的自分泌激活导致细胞生长显著抑制，并伴有细胞在G0/G1期的积累。通过形态变化、β-酪蛋白和α-乳白蛋白等乳蛋白的合成以及脂质小泡的产生确定，这些细胞经历了终末细胞分化。我们的结果表明，Met-HGF/SF这一致癌信号转导通路能够在某些乳腺癌细胞中诱导生长停滞和分化，因此可能具有作为乳腺癌治疗的治疗和/或预后工具的潜力。
