Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells

Naohiro Fujimoto, Hiroshi Miyamoto, Atsushi Mizokami, Shuji Harada, Masayoshi Nomura, Yoichi Ueta, Takakazu Sasaguri, Tetsuro Matsumoto

Research output: Contribution to journalArticle

Abstract

Although androgen-hypersensitivity is one of the possible pathways of hormone-resistance in prostate cancer, the mechanisms of androgen- hypersensitivity are still largely unknown. Using androgen-hypersensitive prostate cancer cells LN-TR2, established from androgen-sensitive LNCaP cells by the long term treatment with tumor necrosis factor α, we explored the mechanisms of androgen-hypersensitivity in prostate cancer cells which may thus play a role in hormone-resistance. We examined the androgen receptor (AR) DNA sequence and the expression levels of AR and 8 AR cofactors in LNCaP and LN-TR2 cells. As a result, no novel mutation was developed in AR DNA in LN-TR2 cells. We observed higher expressions of nuclear AR upon androgen-treatment and 2 AR coactivators, ARA55 and TIF2, in LN-TR2 compared to LNCaP cells. An overexpression of ARA55 or TIF2 enhanced androgen-induced AR transcriptional activity in LNCaP cell. In the presence of those AR coactivators, AR activity was observed even at low concentrations of androgen. In 2 of 6 patients, the expression level of ARA55 was higher in cancer cells in hormone-resistant tumor than those in hormone-sensitive tumor. Taken together, our results suggest that prostate cancer cells change androgen-sensitivity by an overexpression of nuclear AR and AR coactivators, thus, resulting in transition from androgen-dependent to androgen-independent prostate cancer cells. An increase in nuclear AR and AR coactivators may cause androgen-hypersensitivity of prostate cancer cells and thus play a role in hormone-resistance, at least in some patients with prostate cancer.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalCancer Investigation
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Androgen receptor
  • Cofactor
  • Hormone-resistance
  • Prostate cancer
  • TNFα

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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