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 language | English |
|---|---|
| Pages (from-to) | 5117-5125 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Jun 1 2007 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles. / Tamura, Kenji; Furihata, Mutsuo; Tsunoda, Tatsuhiko; Ashida, Shingo; Takata, Ryo; Obara, Wataru; Yoshioka, Hiroki; Daigo, Yataro; Nasu, Yasutomo; Kumon, Hiromi; Konaka, Hiroyuki; Namiki, Mikio; Tozawa, Keiichi; Kohri, Kenjiro; Tanji, Nozomu; Yokoyama, Masayoshi; Shimazui, Toru; Akaza, Hideyuki; Mizutani, Yoichi; Miki, Tsuneharu; Fujioka, Tomoaki; Shuin, Taro; Nakamura, Yusuke; Nakagawa, Hidewaki.
In: Cancer Research, Vol. 67, No. 11, 01.06.2007, p. 5117-5125.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles
AU - Tamura, Kenji
AU - Furihata, Mutsuo
AU - Tsunoda, Tatsuhiko
AU - Ashida, Shingo
AU - Takata, Ryo
AU - Obara, Wataru
AU - Yoshioka, Hiroki
AU - Daigo, Yataro
AU - Nasu, Yasutomo
AU - Kumon, Hiromi
AU - Konaka, Hiroyuki
AU - Namiki, Mikio
AU - Tozawa, Keiichi
AU - Kohri, Kenjiro
AU - Tanji, Nozomu
AU - Yokoyama, Masayoshi
AU - Shimazui, Toru
AU - Akaza, Hideyuki
AU - Mizutani, Yoichi
AU - Miki, Tsuneharu
AU - Fujioka, Tomoaki
AU - Shuin, Taro
AU - Nakamura, Yusuke
AU - Nakagawa, Hidewaki
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34347241757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347241757&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-4040
DO - 10.1158/0008-5472.CAN-06-4040
M3 - Article
C2 - 17545589
AN - SCOPUS:34347241757
VL - 67
SP - 5117
EP - 5125
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 11
ER -