Skip to main content

Advertisement

Log in

Chrebp regulates the transcriptional activity of androgen receptor in prostate cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Androgen receptor (AR), a member of nuclear hormone receptor, plays an essential role in the initiation and progression of prostate cancer (PCa). In the present study, by way of immunoprecipitation followed by mass spectrometry (IP/MS) system, we found that carbohydrate-responsive element-binding protein (Chrebp), a glucose sensor in normal and cancer cells, interacted with AR in LNCaP cells. The interaction was further confirmed by coimmunoprecipitation analysis. Besides, Chrebp is required for the optimal transcriptional activity of AR in promoting the transcription of the prostate-specific antigen (PSA) promoter and messenger RNA (mRNA) expression. Consistently, knockdown of Chrebp using small interfering RNA (siRNA) in LNCaP cells reduced endogenous PSA levels. Together, our study demonstrates that Chrebp interacts with AR and regulates its transcriptional activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aggarwal R, Kurhanewicz J. Prostate cancer in 2013: The changing role of imaging in clinical care. Nat Rev Urol. 2014;11(2):75–7.

    Article  PubMed  Google Scholar 

  2. Bishr M, Saad F. Overview of the latest treatments for castration-resistant prostate cancer. Nat Rev Urol. 2013;10(9):522–8.

    PubMed  Google Scholar 

  3. Saylor PJ. Prostate cancer: the androgen receptor remains front and centre. Nat Rev Clin Oncol. 2013;10(3):126–8.

    Article  CAS  PubMed  Google Scholar 

  4. Chang KH, Sharifi N. Prostate cancer-from steroid transformations to clinical translation. Nat Rev Urol. 2012;9(12):721–4.

    Article  CAS  PubMed  Google Scholar 

  5. Manolagas SC, O’Brien CA, Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol. 2013;9(12):699–712.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000;14(2):121–41.

    CAS  PubMed  Google Scholar 

  7. Jänne OA, Moilanen AM, Poukka H, et al. Androgen-receptor-interacting nuclear proteins. Biochem Soc Trans. 2000;28(4):401–5.

    Article  PubMed  Google Scholar 

  8. Holter E, Kotaja N, Mäkela S, et al. Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Mol Endocrinol. 2002;16(3):515–28.

    Article  CAS  PubMed  Google Scholar 

  9. Filhoulaud G, Guilmeau S, Dentin R, Girard J, Postic C. Novel insights into ChREBP regulation and function. Trends Endocrinol Metab. 2013;24(5):257–68.

    Article  CAS  PubMed  Google Scholar 

  10. Iizuka K. Recent progress on the role of ChREBP in glucose and lipid metabolism. Endocr J. 2013;60(5):543–55.

    Article  CAS  PubMed  Google Scholar 

  11. Yamashita H, Takenoshita M, Sakurai M, et al. A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci U S A. 2001;98(16):9116–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Iizuka K, Bruick RK, Liang G, Horton JD, Uyeda K. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci U S A. 2004;101(19):7281–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Benhamed F, Denechaud PD, Lemoine M, et al. The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J Clin Investig. 2012;122(6):2176–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Tong X, Zhao F, Mancuso A, Gruber JJ, Thompson CB. The glucose-responsive transcription factor ChREBP contributes to glucose-dependent anabolic synthesis and cell proliferation. Proc Natl Acad Sci U S A. 2009;106(51):21660–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Airley RE, McHugh P, Evans AR, et al. Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression. Br J Cancer. 2014;110(3):715–23.

    Article  CAS  PubMed  Google Scholar 

  16. Deng Z, Wan M, Cao P, et al. Yin Yang 1 regulates the transcriptional activity of androgen receptor. Oncogene. 2009;28(42):3746–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Kaulfuss S, Grzmil M, Hemmerlein B, et al. Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells. Mol Endocrinol. 2008;22(7):1606–21.

    Article  CAS  PubMed  Google Scholar 

  18. Gioeli D, Ficarro SB, Kwiek JJ, et al. Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J Biol Chem. 2002;277(32):29304–14.

    Article  CAS  PubMed  Google Scholar 

  19. Ha S, Iqbal NJ, Mita P, et al. Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer. Oncogene. 2013;32(34):3992–4000.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Fu M, Rao M, Wang C, et al. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol Cell Biol. 2003;23(23):8563–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Dongfang Zhaoyang Talent Plan (DFZY-3).

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiao-Fei Wen.

Additional information

Xue-Lei Wang and Xiao-Fei Wen contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

(A-B) mRNA levels of FASN AND L-PK in LNCaP cells with Chrebp overexpression (A) or knockdown (B) (GIF 247 kb)

High resolution image(TIFF 237 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, XL., Wen, XF., Li, RB. et al. Chrebp regulates the transcriptional activity of androgen receptor in prostate cancer. Tumor Biol. 35, 8143–8148 (2014). https://doi.org/10.1007/s13277-014-2085-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2085-8

Keywords

Navigation