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Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.

Publication ,  Journal Article
Wang, Q; Li, W; Zhang, Y; Yuan, X; Xu, K; Yu, J; Chen, Z; Beroukhim, R; Wang, H; Lupien, M; Wu, T; Regan, MM; Meyer, CA; Carroll, JS ...
Published in: Cell
July 23, 2009

The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2009

Volume

138

Issue

2

Start / End Page

245 / 256

Location

United States

Related Subject Headings

  • Ubiquitin-Conjugating Enzymes
  • Transcriptional Activation
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Male
  • Humans
  • Histones
  • Hepatocyte Nuclear Factor 3-alpha
  • Gene Expression Regulation, Neoplastic
  • Developmental Biology
 

Citation

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Wang, Q., Li, W., Zhang, Y., Yuan, X., Xu, K., Yu, J., … Brown, M. (2009). Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell, 138(2), 245–256. https://doi.org/10.1016/j.cell.2009.04.056
Wang, Qianben, Wei Li, Yong Zhang, Xin Yuan, Kexin Xu, Jindan Yu, Zhong Chen, et al. “Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.Cell 138, no. 2 (July 23, 2009): 245–56. https://doi.org/10.1016/j.cell.2009.04.056.
Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, et al. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009 Jul 23;138(2):245–56.
Wang, Qianben, et al. “Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.Cell, vol. 138, no. 2, July 2009, pp. 245–56. Pubmed, doi:10.1016/j.cell.2009.04.056.
Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, Chen Z, Beroukhim R, Wang H, Lupien M, Wu T, Regan MM, Meyer CA, Carroll JS, Manrai AK, Jänne OA, Balk SP, Mehra R, Han B, Chinnaiyan AM, Rubin MA, True L, Fiorentino M, Fiore C, Loda M, Kantoff PW, Liu XS, Brown M. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009 Jul 23;138(2):245–256.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2009

Volume

138

Issue

2

Start / End Page

245 / 256

Location

United States

Related Subject Headings

  • Ubiquitin-Conjugating Enzymes
  • Transcriptional Activation
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Male
  • Humans
  • Histones
  • Hepatocyte Nuclear Factor 3-alpha
  • Gene Expression Regulation, Neoplastic
  • Developmental Biology