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The Ets Transcription Factor ELF5 Functions as a Tumor Suppressor in the Kidney

Published online by Cambridge University Press:  21 February 2012

Erika J. Lapinskas
Affiliation:
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Australia.
Suzanne Svobodova
Affiliation:
Division of Laboratory Medicine, Austin Health, Melbourne, Australia.
Ian D. Davis
Affiliation:
Ludwig Institute for Cancer Research, Austin Health, Melbourne, Australia.
Jonathan Cebon
Affiliation:
Ludwig Institute for Cancer Research, Austin Health, Melbourne, Australia.
Paul J. Hertzog
Affiliation:
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Australia.
Melanie A. Pritchard*
Affiliation:
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Australia; Department of Biochemistry and Molecular Biology, Monash University, Australia. melanie.pritchard@monash.edu
*
*ADDRESS FOR CORRESPONDENCE: Dr Melanie Pritchard, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.

Abstract

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Renal cell carcinoma is an important clinical disease with poorly understood etiology. ELF5 is an epithelial-specific member of the Ets family of transcription factors, characterized by the 80 amino acid Ets domain that binds the purine-rich GGAA/T Ets motif found in the promoter regions of a variety of genes. Since ELF5 is highly expressed in kidney and has been postulated to function as a tumor suppressor, at least in the context of the breast, we investigated its role in kidney cancer. In renal cell carcinoma ELF5 expression was consistently decreased in tumor samples versus normal. ELF5 mRNA was decreased in 94% of lesions tested and ELF5 protein was undetectable in 40/40 kidney-derived carcinomas. Re-expression of the ELF5 gene in 786-O renal carcinoma cells suppressed their tumorigenic capacity in vitro and in vivo. This work is the first to suggest that ELF5 has tumor suppressor activity in the kidney.

Type
Articles
Copyright
Copyright © Cambridge University Press 2011