Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression

Masaki Shiota; Yohei Sekino; Shigehiro Tsukahara; Tatsuro Abe; Fumio Kinoshita; Kenjiro Imada; Shohei Ueda; Miho Ushijima; Shohei Nagakawa; Takashi Matsumoto; Eiji Kashiwagi; Ario Takeuchi; Junichi Inokuchi; Takeshi Uchiumi; Yoshinao Oda; Masatoshi Eto

doi:10.1111/cas.14695

Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression

Masaki Shiota, Yohei Sekino, Shigehiro Tsukahara, Tatsuro Abe, Fumio Kinoshita, Kenjiro Imada, Shohei Ueda, Miho Ushijima, Shohei Nagakawa, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Takeshi Uchiumi, Yoshinao Oda, Masatoshi Eto

Research output: Contribution to journal › Article › peer-review

Abstract

Although Y-box binding protein-1 (YB-1) is known to be overexpressed in prostate cancer, especially castration-resistant prostate cancer (CRPC), the mechanism of its overexpression remains unclear. We aimed to elucidate the mechanism of YB-1 overexpression in CRPC. Gene amplification in CRPC cells and tissues was examined by public database analysis, and digital PCR. The significance of YB-1 amplification for the YB-1/androgen receptor (AR) axis and prognosis was examined by public database analysis and immunohistochemistry. YB-1 amplification was mainly observed in CRPC tissues by public database analysis and confirmed in CRPC cells and tissues by digital PCR. Expression of YB-1 was increased in CRPC tissues compared with treatment-naïve tissues. Furthermore, YB-1 and phosphorylated YB-1 levels were associated with AR and AR V7 expression levels. Finally, YB-1 amplification was associated with poor outcomes in CRPC. Taken together, the present findings suggest that YB-1 amplification contributes to progression to CRPC through regulation of AR and AR V7 expressions, and that YB-1 is a promising therapeutic target in CRPC.

Original language	English
Pages (from-to)	323-330
Number of pages	8
Journal	Cancer Science
Volume	112
Issue number	1
DOIs	https://doi.org/10.1111/cas.14695
Publication status	Published - Jan 2021

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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Shiota, M., Sekino, Y., Tsukahara, S., Abe, T., Kinoshita, F., Imada, K., Ueda, S., Ushijima, M., Nagakawa, S., Matsumoto, T., Kashiwagi, E., Takeuchi, A., Inokuchi, J., Uchiumi, T., Oda, Y., & Eto, M. (2021). Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression. Cancer Science, 112(1), 323-330. https://doi.org/10.1111/cas.14695

Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression. / Shiota, Masaki; Sekino, Yohei; Tsukahara, Shigehiro; Abe, Tatsuro; Kinoshita, Fumio; Imada, Kenjiro; Ueda, Shohei; Ushijima, Miho; Nagakawa, Shohei; Matsumoto, Takashi ; Kashiwagi, Eiji ; Takeuchi, Ario ; Inokuchi, Junichi ; Uchiumi, Takeshi ; Oda, Yoshinao ; Eto, Masatoshi.

In: Cancer Science, Vol. 112, No. 1, 01.2021, p. 323-330.

Research output: Contribution to journal › Article › peer-review

Shiota, M, Sekino, Y, Tsukahara, S, Abe, T, Kinoshita, F, Imada, K, Ueda, S, Ushijima, M, Nagakawa, S, Matsumoto, T , Kashiwagi, E , Takeuchi, A , Inokuchi, J , Uchiumi, T , Oda, Y & Eto, M 2021, 'Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression', Cancer Science, vol. 112, no. 1, pp. 323-330. https://doi.org/10.1111/cas.14695

Shiota, Masaki ; Sekino, Yohei ; Tsukahara, Shigehiro ; Abe, Tatsuro ; Kinoshita, Fumio ; Imada, Kenjiro ; Ueda, Shohei ; Ushijima, Miho ; Nagakawa, Shohei ; Matsumoto, Takashi ; Kashiwagi, Eiji ; Takeuchi, Ario ; Inokuchi, Junichi ; Uchiumi, Takeshi ; Oda, Yoshinao ; Eto, Masatoshi. / Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression. In: Cancer Science. 2021 ; Vol. 112, No. 1. pp. 323-330.

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title = "Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression",

abstract = "Although Y-box binding protein-1 (YB-1) is known to be overexpressed in prostate cancer, especially castration-resistant prostate cancer (CRPC), the mechanism of its overexpression remains unclear. We aimed to elucidate the mechanism of YB-1 overexpression in CRPC. Gene amplification in CRPC cells and tissues was examined by public database analysis, and digital PCR. The significance of YB-1 amplification for the YB-1/androgen receptor (AR) axis and prognosis was examined by public database analysis and immunohistochemistry. YB-1 amplification was mainly observed in CRPC tissues by public database analysis and confirmed in CRPC cells and tissues by digital PCR. Expression of YB-1 was increased in CRPC tissues compared with treatment-na{\"i}ve tissues. Furthermore, YB-1 and phosphorylated YB-1 levels were associated with AR and AR V7 expression levels. Finally, YB-1 amplification was associated with poor outcomes in CRPC. Taken together, the present findings suggest that YB-1 amplification contributes to progression to CRPC through regulation of AR and AR V7 expressions, and that YB-1 is a promising therapeutic target in CRPC.",

author = "Masaki Shiota and Yohei Sekino and Shigehiro Tsukahara and Tatsuro Abe and Fumio Kinoshita and Kenjiro Imada and Shohei Ueda and Miho Ushijima and Shohei Nagakawa and Takashi Matsumoto and Eiji Kashiwagi and Ario Takeuchi and Junichi Inokuchi and Takeshi Uchiumi and Yoshinao Oda and Masatoshi Eto",

note = "Funding Information: This work was supported by a JSPS KAKENHI grant (17K11145) to MS. The funder had no role in study design, data collection, data analysis, interpretation, or writing of the report. We are grateful to Dr Martin Gleave (Vancouver Prostate Centre, Vancouver, BC, Canada) for providing the C4‐2 cells. We thank Ms Mami Nakamizo, Ms Eriko Gunshima, and Ms Noriko Hakoda for technical assistance. We also thank Alison Sherwin, PhD, from Edanz Group for editing a draft of this manuscript. ",

year = "2021",

month = jan,

doi = "10.1111/cas.14695",

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T1 - Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression

AU - Shiota, Masaki

AU - Sekino, Yohei

AU - Tsukahara, Shigehiro

AU - Abe, Tatsuro

AU - Kinoshita, Fumio

AU - Imada, Kenjiro

AU - Ueda, Shohei

AU - Ushijima, Miho

AU - Nagakawa, Shohei

AU - Matsumoto, Takashi

AU - Kashiwagi, Eiji

AU - Takeuchi, Ario

AU - Inokuchi, Junichi

AU - Uchiumi, Takeshi

AU - Oda, Yoshinao

AU - Eto, Masatoshi

N1 - Funding Information: This work was supported by a JSPS KAKENHI grant (17K11145) to MS. The funder had no role in study design, data collection, data analysis, interpretation, or writing of the report. We are grateful to Dr Martin Gleave (Vancouver Prostate Centre, Vancouver, BC, Canada) for providing the C4‐2 cells. We thank Ms Mami Nakamizo, Ms Eriko Gunshima, and Ms Noriko Hakoda for technical assistance. We also thank Alison Sherwin, PhD, from Edanz Group for editing a draft of this manuscript.

PY - 2021/1

Y1 - 2021/1

N2 - Although Y-box binding protein-1 (YB-1) is known to be overexpressed in prostate cancer, especially castration-resistant prostate cancer (CRPC), the mechanism of its overexpression remains unclear. We aimed to elucidate the mechanism of YB-1 overexpression in CRPC. Gene amplification in CRPC cells and tissues was examined by public database analysis, and digital PCR. The significance of YB-1 amplification for the YB-1/androgen receptor (AR) axis and prognosis was examined by public database analysis and immunohistochemistry. YB-1 amplification was mainly observed in CRPC tissues by public database analysis and confirmed in CRPC cells and tissues by digital PCR. Expression of YB-1 was increased in CRPC tissues compared with treatment-naïve tissues. Furthermore, YB-1 and phosphorylated YB-1 levels were associated with AR and AR V7 expression levels. Finally, YB-1 amplification was associated with poor outcomes in CRPC. Taken together, the present findings suggest that YB-1 amplification contributes to progression to CRPC through regulation of AR and AR V7 expressions, and that YB-1 is a promising therapeutic target in CRPC.

AB - Although Y-box binding protein-1 (YB-1) is known to be overexpressed in prostate cancer, especially castration-resistant prostate cancer (CRPC), the mechanism of its overexpression remains unclear. We aimed to elucidate the mechanism of YB-1 overexpression in CRPC. Gene amplification in CRPC cells and tissues was examined by public database analysis, and digital PCR. The significance of YB-1 amplification for the YB-1/androgen receptor (AR) axis and prognosis was examined by public database analysis and immunohistochemistry. YB-1 amplification was mainly observed in CRPC tissues by public database analysis and confirmed in CRPC cells and tissues by digital PCR. Expression of YB-1 was increased in CRPC tissues compared with treatment-naïve tissues. Furthermore, YB-1 and phosphorylated YB-1 levels were associated with AR and AR V7 expression levels. Finally, YB-1 amplification was associated with poor outcomes in CRPC. Taken together, the present findings suggest that YB-1 amplification contributes to progression to CRPC through regulation of AR and AR V7 expressions, and that YB-1 is a promising therapeutic target in CRPC.

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