A New Concept for Androgen Receptor-Independent Growth of Prostate Cancer

4155Angiogenin-mediated rRNA transcriptionplays a role in androgen-independentgrowth of prostate cancer cells Norie Yoshioka, Koji Kishimoto, Wenhao Yu, Miki Katsurano, Takanori Tsuji and Guo-Fu Hu Harvard Medical School, Boston, MA Progression to androgen-independent disease remains the major barrier to effective treatment of prostatecancer. The ability of prostate cancer to acquire an androgen-independent phenotype has been associatedwith changes in androgen receptor (AR). Metastatic hormone refractory prostate cancer has aheterogeneous morphology and phenotype among which AR-deficient cells exist indicating thatalternative pathways can be invoked that are capable of bypassing the AR completely. We hypothesizethat angiogenin-mediated rRNA transcription is one such mechanism. Angiogenin is an angiogenicribonuclease whose expression is upregulated in human prostate cancer tissues and cells. Itsconcentration is progressively increased in the plasma of prostate cancer patients as the diseaseprogresses from androgen-dependent to androgen-independent status. Here we examined the effect ofangiogenin on androgen-independent growth of prostate cancer cells both in vitro and in vivo. Theresults show that exogenous angiogenin stimulates the proliferation of androgen-responsive LNCaP cellsin the absence of androgens and other steroid hormones. However, exogenous angiogenin has no effecton the proliferation of androgen-independent prostate cancer cell lines including PC-3, PC-3M, and DU-145. Knocking down the expression of endogenous angiogenin in PC-3 cells by siRNA resulted in adecrease in rRNA transcription, ribosome biogenesis, and cell proliferation. Soft agar assay shows thatboth the colony number and size decreased in angiogenin siRNA transfectants. exogenous angiogeninwas able to compensate the loss of endogenous angiogenin mediated by siRNA in the colony formationassay. Moreover, tumor therapy experiments show that neamine and neomycin, aminoglycosides thatblock nuclear translocation of angiogenin, inhibit xenografic growth of PC-3 cells in athymic mice.These results demonstrate that angiogenin stimulates androgen-independent growth of prostate cancercells and suggest that angiogenin may play a role in the progression of prostate cancer to androgenindependence. This work was supported by NIH grant CA105241 and DOD grant PC050976 to GFH .HOME HELP FEEDBACK HOW TO CITE ABSTRACTS CME INFORMATION SEARCHQUICK SEARCH:[advanced] GoAuthor:hu,gfKeyword(s): ServicesSimilar articles in this journalDownload to citation managerCiting ArticlesCiting Articles via Google ScholarGoogle ScholarArticles by Yoshioka, N.Articles by Hu, G.-F.Search for Related ContentPubMedArticles by Yoshioka, N.Articles by Hu, G.-F.Cellular and Molecular Biology 55: ExtracellularSignalingPage 1 of 2Angiogenin-mediated rRNA transcription plays a role in androgen-independent growth of... 11/14/2007http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/977-a?maxtoshow=&HI...; Guo-Fu Hu, Ph.D.Harvard Medical SchoolDepartment of Pathology77 Avenue Louis PasteurBoston, MA [email protected]