Molecular cloning of a new transforming gene from a chemically transformed human cell line.
ABSTRACT Molecular cloning of the transforming gene from a chemically transformed human osteosarcoma-derived cell line enables the gene to be mapped to chromosome 7 (7p11.4-7qter) and by this criterion and by direct hybridization to be shown to be unrelated to known oncogenes.
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ABSTRACT: c-Met has been demonstrated as an attractive target in lung cancer therapy. Current studies showed that detection of c-Met status in tumor is critical in Met-targeted therapy. However not all patients are suitable for tissue sample collection. It is important to discover novel surrogate markers to detect c-Met status. In the study, soluble c-Met (s-Met) in plasma from 146 Chinese lung cancer patients and 40 disease-free volunteers was measured by enzyme-linked immunosorbent. In parallel, expression of c-Met in those tumors was also assessed by immunohistochemistry. Results showed that, in 146 lung cancer patients, 93 were c-Met expression positive and 74 of 93 were overexpressed. In c-Met-overexpressed patients, plasma s-Met was significantly increased. And further studies showed that plasma s-Met linearly correlated with c-Met expression in tumor. After tumor was removed in Met-overexpressed patients via resection, plasma s-Met significantly decreased to basal level. In addition, plasma s-Met showed to be poorly correlated with tumor size in Met-overexpressed patients. These results demonstrated that plasma s-Met is a sensitive and reliable marker to detect c-Met overexpression in lung cancers, and it is independent of tumor volume.01/2015; 2015:626578. DOI:10.1155/2015/626578
Article: MET inhibition in lung cancer.[Show abstract] [Hide abstract]
ABSTRACT: Targeted agents have completely changed cancer treatment strategy, leading it from a "one size fits all" approach to a customized therapy. In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming "druggable" only in this last period of time. Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell-cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization. Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis. Met amplification is also described to be linked to EGFR acquired resistance. Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment. This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation.02/2013; 2(1):23-39. DOI:10.3978/j.issn.2218-6751.2012.12.04
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ABSTRACT: c-Met is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor (HGF), activates downstream pathways with diverse cellular functions that are important in organ development and cancer progression. Anomalous c-Met signalling has been described in a variety of cancer types, and the receptor is regarded as a novel therapeutic target. In breast cancer there is a need to develop new treatments, particularly for the aggressive subtypes such as triple-negative and basal-like cancer, which currently lack targeted therapy. Over the last two decades, much has been learnt about the functional role of c-Met signalling in different models of breast development and cancer. This work has been complemented by clinical studies, establishing the prognostic significance of c-Met in tissue samples of breast cancer. While the clinical trials of anti-c-Met therapy in advanced breast cancer progress, there is a need to review the existing evidence so that the potential of these treatments can be better appreciated. The aim of this article is to examine the role of HGF/c-Met signalling in in vitro and in vivo models of breast cancer, to describe the mechanisms of aberrant c-Met signalling in human tissues, and to give a brief overview of the anti-c-Met therapies currently being evaluated in breast cancer patients. We will show that the HGF/c-Met pathway is associated with breast cancer progression and suggest that there is a firm basis for continued development of anti-c-Met treatment, particularly for patients with basal-like and triple-negative breast cancer.Breast cancer research: BCR 01/2015; 17(1):52. DOI:10.1186/s13058-015-0547-6 · 5.88 Impact Factor