Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles

Kenji Tamura, Mutsuo Furihata, Tatsuhiko Tsunoda, Shingo Ashida, Ryo Takata, Wataru Obara, Hiroki Yoshioka, Yataro Daigo, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Konaka, Mikio Namiki, Keiichi Tozawa, Kenjiro Kohri, Nozomu Tanji, Masayoshi Yokoyama, Toru Shimazui, Hideyuki Akaza, Yoichi Mizutani, Tsuneharu MikiTomoaki Fujioka, Taro Shuin, Yusuke Nakamura, Hidewaki Nakagawa

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

One of the most critical issues in prostate cancer clinic is emerging hormone-refractory prostate cancers (HRPCs) and their management. Prostate cancer is usually androgen dependent and responds well to androgen ablation therapy. However, at a certain stage, they eventually acquire androgen-independent and more aggressive phenotype and show poor response to any anticancer therapies. To characterize the molecular features of clinical HRPCs, we analyzed gene expression profiles of 25 clinical HRPCs and 10 hormone-sensitive prostate cancers (HSPCs) by genome-wide cDNA microarrays combining with laser microbeam microdissection. An unsupervised hierarchical clustering analysis clearly distinguished expression patterns of HRPC cells from those of HSPC cells. In addition, primary and metastatic HRPCs from three patients were closely clustered regardless of metastatic organs. A supervised analysis and permutation test identified 36 up-regulated genes and 70 down-regulated genes in HRPCs compared with HSPCs (average fold difference > 1.5; P < 0.0001). We observed overexpression of AR, ANLN, and SNRPE and down-regulation of NR4A1, CYP27A1, and HLA-A antigen in HRPC progression. AR overexpression is likely to play a central role of hormone-refractory phenotype, and other genes we identified were considered to be related to more aggressive phenotype of clinical HRPCs, and in fact, knockdown of these overexpressing genes by small interfering RNA resulted in drastic attenuation of prostate cancer cell viability. Our microarray analysis of HRPC cells should provide useful information to understand the molecular mechanism of HRPC progression and to identify molecular targets for development of HRPC treatment.

Original languageEnglish
Pages (from-to)5117-5125
Number of pages9
JournalCancer Research
Volume67
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tamura, K., Furihata, M., Tsunoda, T., Ashida, S., Takata, R., Obara, W., Yoshioka, H., Daigo, Y., Nasu, Y., Kumon, H., Konaka, H., Namiki, M., Tozawa, K., Kohri, K., Tanji, N., Yokoyama, M., Shimazui, T., Akaza, H., Mizutani, Y., ... Nakagawa, H. (2007). Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles. Cancer Research, 67(11), 5117-5125. https://doi.org/10.1158/0008-5472.CAN-06-4040