Clinical application and functional analysis of the cofactor of androgen receptor in prostate cancer

1)不依赖雄激素的前列腺癌细胞系的建立我们通过活性炭剥离FBS长期培养获得了不依赖雄激素的增殖能力的细胞系。抗雄激素药物在该细胞系中不能显示出生长抑制作用-我们将在未来对该细胞系进行更密切的分析。2)前列腺癌RIZ1基因DNA甲基化分析RIZ1是一种组蛋白甲基转移酶，是与视网膜母细胞瘤蛋白相互作用的锌指基因。42.6%的前列腺癌组织检测到RIZ1基因的DNA甲基化。与Gleason评分较低的PCa标本相比，高Gleason评分的PCa标本中RIZ1的DNA甲基化更频繁。由于DNA甲基化，PC3细胞系显示RIZ1 mRNA的丢失，这种丢失通过去甲基化剂5- aza -2-脱氧胞苷处理得到纠正。这些结果表明，异常DNA甲基化导致RIZ1转录失活可能参与前列腺癌的发生。3)雌激素相关受体（ERR）与鸟嘌呤核苷酸结合蛋白样3 （GNL3L）我们发现ERR与GNL3L的相互作用。ERR和GNL3L在前列腺和前列腺癌组织中表达。GNL3L抑制前列腺癌细胞中ERR3的转录活性。我们将在未来研究ERRs和GNL3L在前列腺癌细胞中的生理功能。

1) Establishment of androgen independent prostate cancer cell lineWe obtained the cell line that acquired the proliferation potency without androgen by culturing under charcoal stripped FBS for a long term. The anti-androgen medicine cannot show the growth inhibition effect in this cell line- We will analyze the cell line more closely in the future.2) Analysis of DNA methylation of the RIZ1 gene in prostate cancerRiz1 is a histone methyltransferase and a retinoblastoma protein-interacting zinc finger gene. DNA methylation of the RIZ1 gene was detected in 42.6% of prostate cancer tissues. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score than in those with a low Gleason score. PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis.3) Estrogen related receptor (ERR) and Guanine nucleotide binding protein-like3 (GNL3L)We found out that the interaction between ERR and GNL3L. ERR and GNL3L express in prostate and prostate cancer tissue. GNL3L inhibits the transcriptional activity of ERR3 in prostate cancer cells. We will research a physiological function of ERRs and GNL3L in the prostate cancer cell in the future.