RRC ID |
45239
|
Author |
Ito S, Ueda T, Ueno A, Nakagawa H, Taniguchi H, Hongo F, Kamoi K, Okihara K, Kawauchi A, Miki T.
|
Title |
Paired box 2 upregulates androgen receptor gene expression in androgen-independent prostate cancer.
|
Journal |
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.
|
Volume |
281(19)
|
Pages |
4506-18
|
Published |
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
|
Times Cited |
6
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Human and Animal Cells |
|