RRC ID 45239
著者 Ito S, Ueda T, Ueno A, Nakagawa H, Taniguchi H, Hongo F, Kamoi K, Okihara K, Kawauchi A, Miki T.
タイトル Paired box 2 upregulates androgen receptor gene expression in androgen-independent prostate cancer.
ジャーナル FEBS J
Abstract 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.
巻・号 281(19)
ページ 4506-18
公開日 2014-10-1
DOI 10.1111/febs.12959
PMID 25132193
MeSH Aged Aged, 80 and over Animals Cell Line, Tumor Cell Proliferation DNA Methylation Epigenesis, Genetic Gene Expression Regulation, Neoplastic* Humans Male Mice Mice, SCID Middle Aged Neoplasm Transplantation Neoplasms, Hormone-Dependent / genetics Neoplasms, Hormone-Dependent / metabolism PAX2 Transcription Factor / physiology* Promoter Regions, Genetic Prostatic Neoplasms / genetics Prostatic Neoplasms / metabolism* Receptors, Androgen / genetics* Receptors, Androgen / metabolism Up-Regulation
IF 4.392
引用数 6
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞