title: Stimulation of prostate cancer cellular proliferation and invasion by the androgen receptor co-activator ARA70.
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 ARA70 alpha and an internally spliced 35-kDa variant termed ARA70 beta. We have previously reported that ARA70 alpha expression is reduced in prostate cancer, and its overexpression inhibits proliferation of LNCaP prostate cancer cells. However, the function of the ARA70 beta isoform in prostate cancer is not understood. In this report we examined the effects of ARA70 beta on AR transcriptional regulation as well as prostate cancer cellular proliferation and invasion. Although both ARA70 alpha and ARA70 beta functioned as transcriptional co-activators of AR in cell-based reporter assays, ARA70 beta overexpression, in contrast to ARA70 alpha, promoted prostate cancer cellular proliferation and invasion through Matrigel. Interestingly, genome-wide expression profiling of cells expressing ARA70 beta revealed an increase in the expression of genes involved in the control of cell division and adhesion, compatible with a role for ARA70 beta in proliferation and invasion. Consistent with its function in promoting cell growth and invasion, ARA70 beta expression was increased in prostate cancer. Our findings implicate ARA70 beta as a regulator of tumor cell growth and metastasis by affecting gene expression.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York Harbor Healthcare System, 423 E. 23rd St., Room 6140N, New York, NY 10010, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.forename: Caihong X
authors.initials: CX
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
authors.forename: Martin
authors.initials: M
authors.lastname: Ligr
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wei
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Garabedian
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000737:chemistry; D011944:Receptors, Androgen / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C410798:AR protein, human; D004338:Drug Combinations; D007797:Laminin; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011509:Proteoglycans; D011944:Receptors, Androgen; D014157:Transcription Factors; C059485:matrigel; D003094:Collagen