Functional analysis of MID1 that may be a candidate as a therapeutic target for castration-resistant prostate cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya City University
• Principal Investigator: TAKAHASHI Satoru 名古屋市立大学, 医学(系)研究科(研究院), 教授 (60254281)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Shugo 名古屋市立大学, 大学院医学研究科, 研究員 (60363933) ; SATO Shinya 名古屋市立大学, 大学院医学研究科, 研究員 (30464564)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 前立腺癌 / MID1/TRIM18

Outline of Final Research Achievements

We have established an androgen-independent (AI) subline from androgen-dependent LNCaP cells, and examined genes differentially expressed between LNCaP and LNCaP-AI by microarray analysis. We thereby found midline 1 (MID1) to be an upregulated gene in the latter. Knockdown of MID1 expression in LNCaP-AI cells resulted in significant suppression of invasion, and enforced expression of MID1 in LNCaP promoted an invasive capacity in the Matrigel chemoinvasion assay. MID1 also promoted AR transcriptional activity in gene dosage-dependent manner by luciferase reporter assay. CRYAB, one of upregulated gene in LNCaP-AI cells, promoted invasive ability and knockdown of it led to suppress invasion of prostate cancer cells in the same as MID1. However, interaction between MID1 and CRYAB did not confirmed by immunocytochemistry. These results suggest that MID1 is an AR coactivator and deeply involved in prostate cancer progression via CRYAB with an indirect manner.

Free Research Field

病理学