Paired box 2 upregulates androgen receptor gene expression in androgen-independent prostate cancer

被引：9

作者：

Ito, Saya ^{[1
]}

Ueda, Takashi ^{[1
]}

Ueno, Akihisa ^{[1
]}

Nakagawa, Hideo ^{[1
]}

Taniguchi, Hidefumi ^{[1
]}

Hongo, Fumiya ^{[1
]}

Kamoi, Kazumi ^{[1
]}

Okihara, Koji ^{[1
]}

Kawauchi, Akihiro ^{[1
]}

Miki, Tsuneharu ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Urol, Kyoto 6028566, Japan

来源：

FEBS JOURNAL | 2014年 / 281卷 / 19期

关键词：

androgen receptor; DNA methylation; gene expression; PAX2; prostate cancer; CARCINOMA-CELL-LINE; UPSTREAM ENHANCER; ANTIGEN PROMOTER; DNA-BINDING; PAX2; METHYLATION; ACTIVATION; REGION; TRANSCRIPTION; RECRUITMENT;

D O I：

10.1111/febs.12959

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Androgen-independent prostate cancer is known as a hormone-refractory disease. Although the androgen receptor (AR) is considered to be a key regulator of androgen-independent prostate cancer progression, the mechanism through which AR gene expression is regulated is not well understood. In the present study, we showed that the AR gene was upregulated by paired box 2 (PAX2) in androgen-independent prostate cancer. When PAX2 upregulated AR gene expression, a decrease in DNA methylation of the AR gene locus was also observed. PAX2 was highly expressed and promoted cell growth in an androgen-independent prostate cancer cell line (22Rv1). The cell growth inhibition by PAX2 knockdown was rescued by AR overexpression in 22Rv1 cells. In a mouse xenograft model of androgen-independent prostate cancer, PAX2 knockdown inhibited tumor growth and AR gene expression and also increased DNA methylation of the AR gene. Consistent with this, AR and PAX2 expression levels were positively correlated in prostate cancer patients. These findings suggested that PAX2 promoted cancer cell growth in androgen-independent prostate cancer by regulating AR gene expression through an epigenetic mechanism.

引用

页码：4506 / 4518

页数：13

共 44 条

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