Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability.

Publication ,  Journal Article
Wang, H; Zhang, C; Rorick, A; Wu, D; Chiu, M; Thomas-Ahner, J; Chen, Z; Chen, H; Clinton, SK; Chan, KK; Wang, Q
Published in: Cancer Res
July 15, 2011

The cell-cycle G(2)-M phase gene UBE2C is overexpressed in various solid tumors including castration-resistant prostate cancer (CRPC). Our recent studies found UBE2C to be a CRPC-specific androgen receptor (AR) target gene that is necessary for CRPC growth, providing a potential novel target for therapeutic intervention. In this study, we showed that the G(1)-S cell-cycle inhibitor-779 (CCI-779), an mTOR inhibitor, inhibited UBE2C mRNA and protein expression in AR-positive CRPC cell models abl and C4-2B. Treatment with CCI-779 significantly decreased abl cell proliferation in vitro and in vivo through inhibition of cell-cycle progression of both G(2)-M and G(1)-S phases. In addition, exposure of abl and C4-2B cells to CCI-779 also decreased UBE2C-dependent cell invasion. The molecular mechanisms for CCI-779 inhibition of UBE2C gene expression involved a decreased binding of AR coactivators SRC1, SRC3, p300, and MED1 to the UBE2C enhancers, leading to a reduction in RNA polymerase II loading to the UBE2C promoter, and attenuation of UBE2C mRNA stability. Our data suggest that, in addition to its ability to block cell-cycle G(1) to S-phase transition, CCI-779 causes a cell-cycle G(2)-M accumulation and an inhibition of cell invasion through a novel UBE2C-dependent mechanism, which contributes to antitumor activities of CCI-779 in UBE2C overexpressed AR-positive CRPC.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

July 15, 2011

Volume

71

Issue

14

Start / End Page

4866 / 4876

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Ubiquitin-Conjugating Enzymes
  • Transfection
  • Transcription, Genetic
  • Sirolimus
  • RNA, Messenger
  • Prostatic Neoplasms
  • Orchiectomy
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, H., Zhang, C., Rorick, A., Wu, D., Chiu, M., Thomas-Ahner, J., … Wang, Q. (2011). CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res, 71(14), 4866–4876. https://doi.org/10.1158/0008-5472.CAN-10-4576
Wang, Hongyan, Chunpeng Zhang, Anna Rorick, Dayong Wu, Ming Chiu, Jennifer Thomas-Ahner, Zhong Chen, et al. “CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability.Cancer Res 71, no. 14 (July 15, 2011): 4866–76. https://doi.org/10.1158/0008-5472.CAN-10-4576.
Wang H, Zhang C, Rorick A, Wu D, Chiu M, Thomas-Ahner J, et al. CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res. 2011 Jul 15;71(14):4866–76.
Wang, Hongyan, et al. “CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability.Cancer Res, vol. 71, no. 14, July 2011, pp. 4866–76. Pubmed, doi:10.1158/0008-5472.CAN-10-4576.
Wang H, Zhang C, Rorick A, Wu D, Chiu M, Thomas-Ahner J, Chen Z, Chen H, Clinton SK, Chan KK, Wang Q. CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res. 2011 Jul 15;71(14):4866–4876.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

July 15, 2011

Volume

71

Issue

14

Start / End Page

4866 / 4876

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Ubiquitin-Conjugating Enzymes
  • Transfection
  • Transcription, Genetic
  • Sirolimus
  • RNA, Messenger
  • Prostatic Neoplasms
  • Orchiectomy
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C