Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus

Molecular Carcinogenesis
C WalkerX Yuan

Abstract

Germline alterations of the human von Hippel-Lindau (VHL) tumor suppressor gene predispose to renal cell carcinoma and a constellation of other tumor types found in VHL disease. This gene is also mutated or deleted in a high proportion of sporadic nonpapillary renal cell carcinomas. In the Eker rat model, spontaneous renal cell carcinoma develops with a high frequency. We therefore investigated the role of this tumor suppressor gene in the development of these hereditary rat tumors. By using reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis, the sequence of the rat VHL gene was determined over the portion of the gene homologous to regions where most mutations in the human VHL gene occur. The sequence homology was 90% and the amino-acid identity 99% between the rat and human genes. A developmental and tumor-specific pattern of expression for the VHL gene was found; a ubiquitous 3.2-kb transcript was expressed in all rat tissues examined (neonatal kidney, lung, liver, brain, heart, kidney, spleen, testis, and stomach), and an additional 4.5-kb transcript was expressed in neonatal kidney and cell lines derived from Eker rat renal cell carcinomas (ERC cell lines). To determine whether mutations in the VHL gene wer...Continue Reading

References

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Citations

Oct 3, 2002·Cancer Letters·Yih-Horng ShiaoDouglas C Wolf
Nov 25, 1998·Journal of the National Cancer Institute·Y H ShiaoG C Hard
Jun 23, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer D CohenSerrine S Lau
Mar 21, 1998·Toxicologic Pathology·C Walker

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