Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells

Kazuaki Kita, Masayuki Shiota, Masako Tanaka, Asuka Otsuka, Masaki Matsumoto, Minoru Kato, Satoshi Tamada, Hiroshi Iwao, Katsuyuki Miura, Tatsuya Nakatani, Shuhei Tomita

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Androgen deprivation therapy is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7. In this study, we investigated the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer cell line LNCaP95 that expresses AR-V7, and explored the mechanism by which Hsp70 regulates AR-FL and AR-V7 expression. Quercetin and VER155008 decreased cell proliferation, increased the proportion of apoptotic cells, and decreased the protein levels of AR-FL and AR-V7. Furthermore, VER155008 decreased AR-FL and AR-V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry identified Y-box binding protein 1 (YB-1) as one of the molecules regulating AR-FL and AR-V7 at the transcription level through interaction with Hsp70. VER155008 decreased the phosphorylation of YB-1 and its localization in the nucleus, indicating that the involvement of Hsp70 in AR regulation might be mediated through the activation and nuclear translocation of YB-1. Collectively, these results suggest that Hsp70 inhibitors have potential anti-tumor activity against CRPC by decreasing AR-FL and AR-V7 expression through YB-1 suppression.

Original languageEnglish
Pages (from-to)1820-1827
Number of pages8
JournalCancer Science
Volume108
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Androgen Receptors
Prostatic Neoplasms
Castration
Quercetin
Androgens
Y-Box-Binding Protein 1
Immunoprecipitation
Mass Spectrometry
Phosphorylation
Cell Proliferation
Cell Line
Messenger RNA
VER 155008
Antibodies
Therapeutics

Keywords

  • Androgen receptor splice variant 7
  • castration-resistant prostate cancer
  • heat shock protein 70
  • heat shock protein 70 inhibitor
  • Y-box binding protein 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. / Kita, Kazuaki; Shiota, Masayuki; Tanaka, Masako; Otsuka, Asuka; Matsumoto, Masaki; Kato, Minoru; Tamada, Satoshi; Iwao, Hiroshi; Miura, Katsuyuki; Nakatani, Tatsuya; Tomita, Shuhei.

In: Cancer Science, Vol. 108, No. 9, 01.09.2017, p. 1820-1827.

Research output: Contribution to journalArticle

Kita, K, Shiota, M, Tanaka, M, Otsuka, A, Matsumoto, M, Kato, M, Tamada, S, Iwao, H, Miura, K, Nakatani, T & Tomita, S 2017, 'Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells' Cancer Science, vol. 108, no. 9, pp. 1820-1827. https://doi.org/10.1111/cas.13318
Kita, Kazuaki ; Shiota, Masayuki ; Tanaka, Masako ; Otsuka, Asuka ; Matsumoto, Masaki ; Kato, Minoru ; Tamada, Satoshi ; Iwao, Hiroshi ; Miura, Katsuyuki ; Nakatani, Tatsuya ; Tomita, Shuhei. / Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. In: Cancer Science. 2017 ; Vol. 108, No. 9. pp. 1820-1827.
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