Authors: Pathirage G. Dharmawardana; Alessio Giubellino; Donald P. Bottaro

Source: Current Molecular Medicine, Volume 4, Number 8, December 2004 , pp. 855-868(14)

Publisher: Bentham Science Publishers

Abstract:

Germline missense mutations in the tyrosine kinase domain of the hepatocyte growth factor / scatter factor (HGF / SF) receptor, c-Met, are thought to be responsible for hereditary papillary renal carcinoma (HPRC) type 1, a form of human kidney cancer. In addition to extensive linkage analysis of HPRC families localizing the HPRC type 1 gene within chromosome 7, the demonstration that individual c-Met mutations reconstituted in cultured cells display enhanced and dysregulated kinase activity, and confer cell transformation and tumorigenicity in mice, solidifies this conclusion. Our prior knowledge of HGF / SF biology and c-Met signaling enabled rapid progress in unraveling the molecular pathogenesis of HPRC type 1, and in laying the framework for the development of novel therapeutics for the treatment of this cancer. At the same time, the study of HPRC type 1 has refined our appreciation of the oncogenic potential of c-Met signaling, and challenges our current understanding of HGF / SF and c-Met function in health and disease.

Keywords: c-met; hgf/sf; hprc; missense mutations; renal carcinoma

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1566524043359674

Affiliations: 1: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bldg 10 Rm 2B47, 9000 Rockville Pike, Bethesda, MD 20892-1501, USA.

Publication date: 2004-12-01

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• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

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