Published online before print December 21, 2007

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(American Journal of Pathology. 2008;172:225-235.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070065

Stimulation of Prostate Cancer Cellular Proliferation and Invasion by the Androgen Receptor Co-Activator ARA70β

Yi Peng^*, Caihong X. Li^*, Fei Chen^*, Zhengxin Wang, Martin Ligr^*, Jonathan Melamed^*, Jianjun Wei^*, William Gerald, Michele Pagano^*, Michael J. Garabedian and Peng Lee^*,¶

From the Departments of Pathology,^*and Microbiology and Urology,New York University School of Medicine, New York, New York; the New York Harbor Healthcare System,^¶New York, New York; the Department of Pathology,Memorial Sloan Kettering Cancer Center, New York, New York; and the Department of Cancer Biology,The University of Texas, M.D. Anderson Cancer Center, Houston, Texas

ARA70 was first identified as a gene fused to the ret oncogene in thyroid carcinoma and subsequently as a co-activator for androgen receptor (AR). Two isoforms of ARA70 have been identified: a 70-kDa version called ARA70 and an internally spliced 35-kDa variant termed ARA70β. We have previously reported that ARA70 expression is reduced in prostate cancer, and its overexpression inhibits proliferation of LNCaP prostate cancer cells. However, the function of the ARA70β isoform in prostate cancer is not understood. In this report we examined the effects of ARA70β on AR transcriptional regulation as well as prostate cancer cellular proliferation and invasion. Although both ARA70 and ARA70β functioned as transcriptional co-activators of AR in cell-based reporter assays, ARA70β overexpression, in contrast to ARA70, promoted prostate cancer cellular proliferation and invasion through Matrigel. Interestingly, genome-wide expression profiling of cells expressing ARA70β revealed an increase in the expression of genes involved in the control of cell division and adhesion, compatible with a role for ARA70β in proliferation and invasion. Consistent with its function in promoting cell growth and invasion, ARA70β expression was increased in prostate cancer. Our findings implicate ARA70β as a regulator of tumor cell growth and metastasis by affecting gene expression.