Skip to main content

Advertisement

SpringerLink
Log in

Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5–18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gillam MP, Molitch ME, Lombardi G, Colao A (2006) Advances in the treatment of prolactinomas. Endocr Rev 27:485–534. doi:10.1210/er.2005-9998

    Article  CAS  PubMed  Google Scholar 

  2. Iyer P, Molitch ME (2011) Positive prolactin response to bromocriptine in 2 patients with cabergoline-resistant prolactinomas. Endocr Pract 17:e55–e58. doi:10.4158/EP10369.CR

    Article  PubMed  Google Scholar 

  3. Molitch ME (2005) Pharmacologic resistance in prolactinoma patients. Pituitary 8:43–52. doi:10.1007/s11102-005-5085-2

    Article  CAS  PubMed  Google Scholar 

  4. Oh MC, Aghi MK (2011) Dopamine agonist-resistant prolactinomas. J Neurosurg 114:1369–1379. doi:10.3171/2010.11.jns101369

    Article  CAS  PubMed  Google Scholar 

  5. Wu ZB, Zheng WM, Su ZP, Chen Y, Wu JS, Wang CD, Lin C, Zeng YJ, Zhuge QC (2010) Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior. J Neurooncol 99:25–32. doi:10.1007/s11060-009-0107-y

    Article  CAS  PubMed  Google Scholar 

  6. Liu X, Ma S, Yao Y, Li G, Feng M, Deng K, Dai C, Cai F, Li Y, Zhang B, Wang R (2012) Differential expression of folate receptor alpha in pituitary adenomas and its relationship to tumor behavior. Neurosurgery 70:1274–1280. doi:10.1227/NEU.0b013e3182417e76; discussion 1280

    Article  PubMed  Google Scholar 

  7. Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL, Gao CF, Zhang FR, Wang F, Sun SH (2011) Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology 54:1679–1689. doi:10.1002/hep.24563

    Article  CAS  PubMed  Google Scholar 

  8. Hoischen A, van Bon BW, Gilissen C, Arts P, van Lier B, Steehouwer M, de Vries P, de Reuver R, Wieskamp N, Mortier G, Devriendt K, Amorim MZ, Revencu N, Kidd A, Barbosa M, Turner A, Smith J, Oley C, Henderson A, Hayes IM, Thompson EM, Brunner HG, de Vries BB, Veltman JA (2010) De novo mutations of SETBP1 cause Schinzel–Giedion syndrome. Nat Genet 42:483–485. doi:10.1038/ng.581

    Article  CAS  PubMed  Google Scholar 

  9. Lu R, Gao H, Wang H, Cao L, Bai J, Zhang Y (2013) Overexpression of the Notch3 receptor and its ligand Jagged1 in human clinically non-functioning pituitary adenomas. Oncol Lett 5:845–851. doi:10.3892/ol 2013.1113

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP, Kordon C, Peillon F, Jaquet P, Enjalbert A (1989) Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab 69:500–509

    Article  CAS  PubMed  Google Scholar 

  11. Kukstas LA, Domec C, Bascles L, Bonnet J, Verrier D, Israel JM, Vincent JD (1991) Different expression of the two dopaminergic D2 receptors, D2415 and D2444, in two types of lactotroph each characterised by their response to dopamine, and modification of expression by sex steroids. Endocrinology 129:1101–1103

    Article  CAS  PubMed  Google Scholar 

  12. Caccavelli L, Feron F, Morange I, Rouer E, Benarous R, Dewailly D, Jaquet P, Kordon C, Enjalbert A (1994) Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas. Neuroendocrinology 60:314–322

    Article  CAS  PubMed  Google Scholar 

  13. Azen E, Prakobphol A, Fisher SJ (1993) PRB3 null mutations result in absence of the proline-rich glycoprotein Gl and abolish Fusobacterium nucleatum interactions with saliva in vitro. Infect Immun 61:4434–4439

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Scully C, Bagan JV, Hopper C, Epstein JB (2008) Oral cancer: current and future diagnostic techniques. Am J Dent 21:199–209

    PubMed  Google Scholar 

  15. Raponi M, Zhang Y, Yu J, Chen G, Lee G, Taylor JM, Macdonald J, Thomas D, Moskaluk C, Wang Y, Beer DG (2006) Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res 66:7466–7472. doi:10.1158/0008-5472.CAN-06-1191

    Article  CAS  PubMed  Google Scholar 

  16. Warner TF, Azen EA (1988) Tannins, salivary proline-rich proteins and oesophageal cancer. Med Hypotheses 26:99–102

    Article  CAS  PubMed  Google Scholar 

  17. Pellegrini-Bouiller I, Morange-Ramos I, Barlier A, Gunz G, Figarella-Branger D, Cortet-Rudelli C, Grisoli F, Jaquet P, Enjalbert A (1996) Pit-1 gene expression in human lactotroph and somatotroph pituitary adenomas is correlated to D2 receptor gene expression. J Clin Endocrinol Metab 81:3390–3396

    Article  CAS  PubMed  Google Scholar 

  18. Delgrange E, Sassolas G, Perrin G, Jan M, Trouillas J (2005) Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance. Acta neurochir 147:751–757. doi:10.1007/s00701-005-0498-2; discussion 757–758

    Article  CAS  PubMed  Google Scholar 

  19. Raverot G, Wierinckx A, Dantony E, Auger C, Chapas G, Villeneuve L, Brue T, Figarella-Branger D, Roy P, Jouanneau E, Jan M, Lachuer J, Trouillas J (2010) Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J Clin Endocrinol Metab 95:1708–1716. doi:10.1210/jc.2009-1191

    Article  CAS  PubMed  Google Scholar 

  20. Dehdashti AR, Ganna A, Karabatsou K, Gentili F (2008) Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 62:1006–1015. doi:10.1227/01.neu.0000325862.83961.12; discussion 1015–1007

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Fei Wang, Hua Gao, Chuzhong Li, Runchun Lu, Lei Cao, Yongtu Wu & Yazhuo Zhang

  2. Neurosurgical Department of Beijing Tiantan Hospital, Beijing, China

    Jiwei Bai

  3. Tsinghua University, Beijing, China

    Lichuan Hong

  4. Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur, China

    Yonggang Wu

  5. Neurosurgical Department, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China

    Xiaolei Lan

  6. Capital Medical University, Beijing, China

    Yonggang Wu & Xiaolei Lan

Authors
  1. Fei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chuzhong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiwei Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Runchun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lei Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongtu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lichuan Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yonggang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiaolei Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yazhuo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yazhuo Zhang.

Additional information

Fei Wang and Hua Gao have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 421 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, F., Gao, H., Li, C. et al. Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas. J Neurooncol 116, 83–88 (2014). https://doi.org/10.1007/s11060-013-1276-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-013-1276-2

Keywords

Search

Navigation