Maggiora Piera, Lorenzato Annalisa, Fracchioli Stefano, Costa Barbara, Castagnaro Massimo, Arisio Riccardo, Katsaros Dionyssios, Massobrio Marco, Comoglio Paolo M, Flavia Di Renzo Maria
Laboratory of Cancer Genetics of the Institute for Cancer Research and Treatment, University of Torino School of Medicine, SP 142, Km 3.95, 10060 Candiolo (Torino), Italy.
Exp Cell Res. 2003 Aug 15;288(2):382-9. doi: 10.1016/s0014-4827(03)00250-7.
RON is a member of the receptor tyrosine kinase gene family that includes the MET oncogene, whose germline mutations have been causally related to human tumorigenesis. In vitro, RON and MET receptors cross-talk, synergize in intracellular signaling, and cooperate in inducing morphogenic responses. Here we show that the RON and MET oncogenes were expressed in 55% and 56% of human ovarian carcinomas, respectively, and were significantly coexpressed in 42% (P < 0.001). In ovarian carcinoma samples and cell lines we did not find mutations in RON and MET gene kinase domain, nor coexpression of RON and MET receptor ligands (MSP and HGF, respectively). We show that motility and invasiveness of ovarian cancer cells coexpressing MET and RON receptors were elicited by HGF and, to a lesser extent, by MSP. More interestingly, invasion of both reconstituted basement membrane and collagen gel was greatly enhanced by the simultaneous addition of the two ligands. These data suggest that coexpression of the MET and RON receptors confer a selective advantage to ovarian cancer cells and might promote ovarian cancer progression.
RON是受体酪氨酸激酶基因家族的成员，该家族包括MET癌基因，其种系突变与人类肿瘤发生有因果关系。在体外，RON和MET受体相互作用，在细胞内信号传导中协同作用，并共同诱导形态发生反应。我们在此表明，RON和MET癌基因分别在55%和56%的人类卵巢癌中表达，且在42%的病例中显著共表达（P < 0.001）。在卵巢癌样本和细胞系中，我们未发现RON和MET基因激酶结构域的突变，也未发现RON和MET受体配体（分别为MSP和HGF）的共表达。我们发现，共表达MET和RON受体的卵巢癌细胞的运动性和侵袭性由HGF引发，在较小程度上也由MSP引发。更有趣的是，同时添加这两种配体可大大增强对重组基底膜和胶原凝胶的侵袭。这些数据表明，MET和RON受体的共表达赋予卵巢癌细胞选择性优势，并可能促进卵巢癌进展。
