Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: Involvement of increased AR expression and decreased IGF1 expression

Kiyoshi Takahara, Haruhito Azuma, Takeshi Sakamoto, Satoshi Kiyama, Teruo Inamoto, Naokazu Ibuki, Takeshi Nishida, Hayahito Nomi, Takanobu Ubai, Naoki Segawa, Yoji Katsuoka

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25 Citations (Scopus)

Abstract

Androgen-independent prostate cancer eventually develops metastasis, and radical treatment may not be possible for patients at this stage. In this study, we examined the gene-expression profiles of two prostate cancer cell lines, LNCaP (androgen-dependent) and C4-2 (androgen-independent), using cDNA-microarray hybridization. We focused on the expression of α-methylacyl-CoA racemase (AMACR), whose expression is much higher in C4-2 than in LNCaP, and investigated its biological role in acquisition of androgen-independent cancer growth. Immunohistochemistry and Western blot analysis of subcellular fractions revealed that AMACR expression was much stronger in C4-2 than in LNCaP. Inhibition of AMACR expression using AMACR-siRNA induced an increase in the expression of androgen receptor (AR) and B-cell translocation gene 1, along with a decrease in the expression of genes associated with cancer progression, including insulin-like growth factor I and platelet-derived growth factor alpha, in C4-2 with compared to non-treated C4-2. BrdU analysis and MTT assay demonstrated that AMACR inhibition induced a significant decrease of cell viability in C4-2 when cultured in androgen-depleted serum, becoming consistent with that of LNCaP, suggesting that AMACR inhibition may induce an increase in the expression of AR and characteristic conversion of prostate cancer cells from hormone independency to hormone dependency. We suggest that AMACR inhibition may be a new strategy for treatment of patients with hormone-refractory prostate cancer.

Original languageEnglish
Pages (from-to)2497-2505
Number of pages9
JournalAnticancer Research
Volume29
Issue number7
Publication statusPublished - 01-07-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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    Takahara, K., Azuma, H., Sakamoto, T., Kiyama, S., Inamoto, T., Ibuki, N., Nishida, T., Nomi, H., Ubai, T., Segawa, N., & Katsuoka, Y. (2009). Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: Involvement of increased AR expression and decreased IGF1 expression. Anticancer Research, 29(7), 2497-2505.