title: Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression.
abstract: The androgen receptor (AR) is well known to play a central role in the pathogenesis of prostate cancer (PCa). In several studies, AR was overexpressed in castration-resistant PCa (CRPC). However, the mechanism of AR overexpression in CRPC is not fully elucidated. Y-box binding protein-1 (YB-1) is a pleiotropic transcription factor that is upregulated in CPRC. We aimed to elucidate the role of YB-1 in castration resistance of PCa and identify therapeutic potential of targeting YB-1. Using immunohistochemistry, we found that nuclear YB-1 expression significantly correlated with the Gleason score and AR expression in PCa tissues. In PCa cells, YB-1 regulated AR expression at the transcriptional level. Furthermore, YB-1 expression and nuclear localization were upregulated in CRPC cells. Overexpression of AR, as well as YB-1, conferred castration-resistant growth in LNCaP and 22Rv1 cells. Conversely, knocking down YB-1 resulted in suppressed cell growth and induced apoptosis, which was more efficient than knocking down AR in LNCaP cells. In other types of PCa cells, such as CRPC cells, knocking down YB-1 resulted in a significant reduction of cell growth. In conclusion, these findings suggested that YB-1 induces castration resistance in androgen-dependent PCa cells via AR expression. Thus, YB-1 may be a promising therapeutic target for PCa, as well as CRPC.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.forename: YooHyun
authors.initials: Y
authors.lastname: Song
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kuroiwa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009919:Orchiectomy; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014183:Transplantation, Heterologous; D017211:Treatment Failure; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D011944:Receptors, Androgen; D051840:Y-Box-Binding Protein 1