Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related genes

British Journal of Cancer
S C CliffordE R Maher

Abstract

Hepatocyte growth factor (HGF/SF) is a potent renal proximal tubular cell (PTEC) mitogen involved in renal development. HGF/SF is the functional ligand for the c-met proto-oncogene, and germline c-met mutations are associated with familial papillary renal cell carcinoma. Somatic von Hippel-Lindau disease tumour-suppressor gene (VHL) mutations are frequently detected in sporadic clear cell renal cell carcinomas (RCC), and germline VHL mutations are the commonest cause of familial clear cell RCC. pVHL binds to the positive regulatory components of the trimeric elongin (SIII) complex (elongins B and C) and has been observed to deregulate expression of the vascular endothelial growth factor (VEGF) gene. HGF/SF has similarly been reported to up-regulate expression of the VEGF gene in non-renal experimental systems. To investigate the mechanism of HGF/SF action in PTECs and, specifically, to examine potential interactions between the HGF/c-met and the VHL-mediated pathways for renal tubular growth control, we have isolated untransformed PTECs from normal kidneys, developed conditions for their culture in vitro and used these cells to investigate changes in mRNA levels of the VHL, elongin A, B and C, VEGF, c-myc, c-fos and c-met genes...Continue Reading

Citations

Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H YoshijiH Fukui
Nov 1, 2008·Cancer·Doo-Sik KongDo-Hyun Nam
Oct 8, 2005·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Sarangarajan RanganathanSatdarshan P S Monga
Nov 9, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nick W LiuGennady Bratslavsky
Aug 1, 2000·Kidney International·C Westenfelder, R L Baranowski
Dec 21, 2004·Critical Reviews in Oncology/hematology·Wen G JiangToshikazu Nakamura

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