This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-3821v1 69/8/3347    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, K. Articles by Pestell, R. G. Search for Related Content PubMed PubMed Citation Articles by Wu, K. Articles by Pestell, R. G.

The Cell Fate Determination Factor Dachshund Inhibits Androgen Receptor Signaling and Prostate Cancer Cellular Growth

¹ Department of Cancer Biology, Kimmel Cancer Center and ² Department of Pathology, Thomas Jefferson University, Bluemle Life Sciences Building, Philadelphia, Pennsylvania; and ³ Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York

Requests for reprints: Richard Pestell or Kongming Wu, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107. Phone: 215-503-5692; Fax: 215-503-9334; E-mail: Richard.Pestell{at}jefferson.edu or Kongming.Wu{at}jefferson.edu.

Key Words: DACH1 • AR • prostate cancer • proliferation

Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in human prostate cancer. DACH1 inhibited prostate cancer cellular DNA synthesis, growth in colony forming assays, and blocked contact-independent growth in soft agar assays. DACH1 inhibited androgen receptor (AR) activity, requiring a conserved DS Domain (Dachshund domain conserved with Ski/Sno) that bound NCoR/HDAC and was recruited to an androgen-responsive gene promoter. DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. These studies show a role for the Retinal Determination Gene Network in regulating cellular growth and signaling in prostate cancer. [Cancer Res 2009;69(8):3347–55]

This article has been cited by other articles:

				R. N. Margolis, D. D. Moore, T. M. Willson, and R. K. Guy Chemical Approaches to Nuclear Receptors in Metabolism Sci. Signal., August 4, 2009; 2(82): mr5 - mr5. [Abstract] [Full Text] [PDF]