Real-time imaging analysis of androgen receptor function in hormone refractory Prostate cancer

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: UKIMURA Osamu Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Assistant Professor, 医学研究科, 助手 (70275220)
• Co-Investigator(Kenkyū-buntansha): KAWAUCHI Akihiro Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Associate Professor, 医学研究科, 助教授 (90240952) ; MIKI Tsuneharu Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Professor, 医学研究科, 教授 (10243239) ; KAWATA Mitsuhiro Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Professor, 医学研究科, 教授 (60112512) ; NOMOTO Tsuyoshi Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Assistant Professor, 医学研究科, 助手 (20301426) ; MIZUTANI Yoichi Kyoto Prefectural University of Medicine, Graduate School o f Medical Science, Assistant Professor, 医学研究科, 講師 (10243031)
• Project Period (FY): 2002 – 2003
• Keywords: Prostate cancer / androgen receptor / green fluorescent protein / hormone refractory Prostate cancer

Research Abstract

Androgen has been shown to promote cell proliferation of prostate cancer through the action of androgen receptor (AIR) that is a number of the nuclear receptor superfamily. In a prostate cancer cell line, LNCaP, a point mutation (T877A) is found in AR gene, and it has been supposed that this mutation would be involved in hypersensitivity for low concentration of androgen. In the present study, trafficking of AR and AR(T877A) in living prostate and non-prostate cancer cell lines under various concentration of the ligands was examined by tagging green fluorescent protein (GFP) to the receptors. In a non-prostate cancer cell line, COS-1,wild type AR and mutant AR were differentially localized in the absence of ligand ; AR was completely localized in cytoplasm, but AR(T877A) was localized in cytoplasm and nucleus. In contrast, both AR and AR(T877A) were localized in cytoplasm and nucleus in LNCaP. Upon the addition of the ligand, both type of the receptors that localized in the cytoplasm were translocated into the nucleus in the both cell lines. Moreover, in the presence of low concentration of androgen, the translocation was observed in LNCaP cells, but not in COS-1 cells, and there was no significant difference in the translocation pattern between wild type AR and mutant AR. These results suggest that hypersensitivity of AR may be affected by intracellular factors, such as co-factors and crosstalk with another signal pathway, more than the mutation of AR gene. Real-time imaging with GFP was a promising tool for the investigation of molecular mechanism of hormone refractory appearance prostate cancer.