Suppression of Tak1 Promotes Prostate Tumorigenesis

Overview

Journal Cancer Res

Specialty Oncology

Date 2012 Apr 3

PMID 22467172

Citations 35

Authors

Min Wu

Lihong Shi

Adela Cimic

Lina Romero

Guangchao Sui

Cynthia J Lees

J Mark Cline

Darren F Seals

Joseph S Sirintrapun

Thomas P McCoy

Wennuan Liu

Jin Woo Kim

Gregory A Hawkins

Donna M Peehl

Jianfeng Xu

Scott D Cramer

Affiliations

Soon will be listed here.

Abstract

More than 30% of primary prostate cancers contain a consensus deletion of an approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes TGF-β activated kinase-1 (Tak1), is a putative prostate tumor suppressor gene within this region whose precise function remains obscure. In this study, we investigated the role of Tak1 in human and murine prostate cancers. In 50 well-characterized human cancer specimens, we found that Tak1 expression was progressively lost with increasing Gleason grade, both within each cancer and across all cancers. In murine prostate stem cells and Tak1-deficient prostatic epithelial cells, Tak1 loss increased proliferation, migration, and invasion. When prostate stem cells attenuated for Tak1 were engrafted with fetal urogenital mesenchyme, the histopathology of the grafts reflected the natural history of prostate cancer leading from prostatic intraepithelial neoplasia to invasive carcinoma. In the grafts containing Tak1-suppressed prostate stem cells, p38 and c-jun-NH(2)-kinase activity was attenuated and proliferation was increased. Together, our findings functionally validate the proposed tumor suppressor role of Tak1 in prostate cancer.

Citing Articles

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