Increased susceptibility to in vitro transformation of cells carrying the Eker tumor susceptibility mutation.

Journal Article

Rats carrying the Eker tumor susceptibility mutation are genetically predisposed to renal cell carcinoma. Rats heterozygous for the Eker mutation (Eker carriers) develop multiple bilateral renal cell carcinomas by the age of 1 year. Using an in vitro rat kidney epithelial (RKE) transformation assay developed in our laboratory, proximal tubule cells derived from known Eker rat carriers (+/ek) and non-carriers (+/+) were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), to determine if cells derived from Eker carriers were more susceptible to in vitro transformation than cells derived from non-carrier animals. The percent transformation frequency following MNNG treatment was 7.5-fold higher in cells derived from carrier animals when compared to cells from non-carrier animals. This increased susceptibility to transformation due to inheritance of the Eker mutation is consistent with a predisposition resulting from inactivation of a tumor suppressor gene. The increased susceptibility of kidney epithelial cells carrying the Eker mutation may prove useful in the further development of the RKE transformation assay as a sensitive tool to identify potential renal carcinogens. In addition, because transformation frequency in the RKE assay measures a very early step in multistage transformation, these results also suggest that alterations (by Loss of Heterozygosity or mutation) at the Eker tumor susceptibility locus are an early event in the development of renal tumors in the rat.

Full Text

Duke Authors

Cited Authors

  • Horesovsky, G; Ginsler, J; Everitt, J; Walker, C

Published Date

  • October 1994

Published In

Volume / Issue

  • 15 / 10

Start / End Page

  • 2183 - 2187

PubMed ID

  • 7955051

Electronic International Standard Serial Number (EISSN)

  • 1460-2180

International Standard Serial Number (ISSN)

  • 0143-3334

Digital Object Identifier (DOI)

  • 10.1093/carcin/15.10.2183

Language

  • eng