期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1997
卷号：94
期号：2
页码：701-706
DOI：10.1073/pnas.94.2.701
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived, multifunctional paracrine regulator possessing mitogenic, motogenic, and morphogenetic activities in cultured epithelial cells containing its tyrosine kinase receptor, Met. c-met has been implicated in oncogenesis through correlation of expression with malignant phenotype in specific cell lines and tumors. Paradoxically, however, HGF/SF can also inhibit the growth of some tumor cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were created such that HGF/SF was inappropriately targeted to a variety of tissues. HGF/SF transgenic mice developed a remarkably broad array of histologically distinct tumors of both mesenchymal and epithelial origin. Many neoplasms arose from tissues exhibiting abnormal development, including the mammary gland, skeletal muscle, and melanocytes, suggesting a functional link between mechanisms regulating morphogenesis and those promoting tumorigenesis. Most neoplasms, especially melanomas, demonstrated overexpression of both the HGF/SF transgene and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of normal mesenchymal-epithelial paracrine regulation through the forced misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent malignant transformation of cells of diverse origin.
关键词：autocrine loop ; breast cancer ; malignant melanoma ; Met ; transgenic mice
