title: Paired box 2 upregulates androgen receptor gene expression in androgen-independent prostate cancer.
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.
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.forename: Akihisa
authors.initials: A
authors.lastname: Ueno
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hongo
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kamoi
authors.forename: Koji
authors.initials: K
authors.lastname: Okihara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawauchi
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D011944:Receptors, Androgen
keywords: DNA methylation; PAX2; androgen receptor; gene expression; prostate cancer