Abstract
Abstract The level of HMGA1 is low in androgen-dependent prostate cancer cell line (LNCaP), but is high in androgen-independent prostate cancer cell lines (DU145, PC-3). We have reported that the level of HMGA1 expression in prostate cancer cells is correlated with the extent of chromosomal aberrations (Can Res, 2002) and that transfection of HMGA1 into prostate cancer cell lines induces unbalanced chromosomal rearrangement and expression of matrix metalloproteinase 2 (Prostate, 2004). This suggests that HMGA1 is a strong candidate gene playing a potential role in the progression of prostate cancer. These findings have prompted us to evaluate the effect of HMGA1 on androgen independency, which is associated with the progression of prostate cancer. The androgen-dependent LNCaP cell line was induced to an androgen-independent subline (LN95) by being maintained for long term in the absence of androgen. The absence of androgen induced a 2.5-fold increase in the level of HMGA1 in the LN95 cell line. Androgen deprivation in vitro for 4 days as well as that for 8 days in vivo induced significant increase in the level of HMGA1 in parental LNCaP. On the other hand, the level of HMGA1 in normal prostate of mice 4 days and 11 days after castration as well as sham operation was almost undetectable. The cell proliferation rates of LNCaP cell transfected with HMGA1a vector (LN-H1) and LNCaP cell transfected with control empty vector (LN-EV) were determined with various concentrations (0-1nM) of dihydrotestosterone (DHT) by WST-8 assay in order to examine the effect of HMGA1 on androgen sensitivity. The expression of HMGA1 protein in LNH1 was confirmed to be 3.2-fold as high as that in LNEV. In low concentration (0-0.01 nM) of DHT, LNEV cell could not keep proliferation over day 6, while LNH1 could maintain proliferation over day 6. The cell proliferation rate at day 8 of LN-H1 grown in low concentration (0-0.01 nM) of DHT was about 2-fold higher than that of LN-EV. In contrast, both LN-H1 and LN-EV cells grew equally well in higher concentrations (0.1-1 nM) of DHT and could also keep proliferation over day6. Suppression of HMGA1 in DU145 and PC-3 by siRNA decreased cell proliferation rate and colony formation ability by 40% and 10-fold, respectively, in androgen-deprived medium. These data suggest that HMGA1 is associated with the transition of prostate cancer cells from androgen-sensitive to androgen-independent growth and plays a role in the cell growth of androgen-independent prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 73. doi:1538-7445.AM2012-73
Published Version
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