Stimulation of prostate cancer cellular proliferation and invasion by the androgen receptor co-activator ARA70β

Abstract

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 ARA70α and an internally spliced 35-kDa variant termed ARA70β. We have previously reported that ARA70α 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 ARA70α and ARA70β functioned as transcriptional co-activators of AR in cell-based reporter assays, ARA70β overexpression, in contrast to ARA70α, 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. Copyright © American Society for Investigative Pathology.