Somatic single hits inactivate the X-linked tumor suppressor FOXP3 in the prostate.

Published

Journal Article

Despite clear epidemiological and genetic evidence for X-linked prostate cancer risk, all prostate cancer genes identified are autosomal. Here, we report somatic inactivating mutations and deletion of the X-linked FOXP3 gene residing at Xp11.23 in human prostate cancer. Lineage-specific ablation of FoxP3 in the mouse prostate epithelial cells leads to prostate hyperplasia and prostate intraepithelial neoplasia. In both normal and malignant prostate tissues, FOXP3 is both necessary and sufficient to transcriptionally repress cMYC, the most commonly overexpressed oncogene in prostate cancer as well as among the aggregates of other cancers. FOXP3 is an X-linked prostate tumor suppressor in the male. Because the male has only one X chromosome, our data represent a paradigm of "single genetic hit" inactivation-mediated carcinogenesis.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Liu, R; Li, W; Chen, C; Katoh, H; Chen, G-Y; McNally, B; Lin, L; Zhou, P; Zuo, T; Cooney, KA; Liu, Y; Zheng, P

Published Date

  • October 2009

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 336 - 346

PubMed ID

  • 19800578

Pubmed Central ID

  • 19800578

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2009.08.016

Language

  • eng