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Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

Invasive prolactinomas are more likely to be resistant to drug therapy but the mechanism of this is still unknown. The objective of this study was to analyze the different expression of ERmRNA and D2RmRNA isoforms in prolactinomas responsive and resistant to dopamine agonist (DA), and to discuss the correlation of such gene expression with tumor biological behavior. A prospective study of 20 consecutive patients who harbored prolactinomas was designed. Patients were classified as responsive (14 cases) or resistant (six cases) according to their clinical and biochemical response to bromocriptine. Tumor tissue samples were examined by means of QRT–PCR analysis. Median D2SmRNA expression in responsive patients was about 2.5-fold that in resistant ones (13.5 ± 10.4 and 5.4 ± 2.4, respectively, P = 0.09). No significant difference was found between D2LmRNA expression levels (P = 0.77). However, there was a significant difference between D2S/D2LmRNA ratios for responsive and resistant tumors (P = 0.012). A significant difference was not found between these two groups in levels of ERαmRNA and ERβmRNA expression (P = 0.20 and 0.06, respectively). D2SmRNA expression was significantly different for invasive and noninvasive tumors (6.2 ± 3.6 vs. 17.0 ± 11.2, respectively, P = 0.02). The D2S/D2L ratio is related to the responsiveness of prolactinomas to DA medication, in which D2SmRNA plays an important role. Lower expression of D2SmRNA in invasive tumor patients suggests that invasive prolactinomas may be more likely to be resistant to DA medication.

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Abbreviations

D2R:

Dopamine D2 receptor

D2S:

Dopamine D2 receptor short form

D2L:

Dopamine D2 receptor long form

DA:

Dopamine agonist

ER:

Estrogen receptor

CS:

Cavernous sinus

QRT-PCR:

Quantitative reverse transcriptase-polymerase chain reaction

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Acknowledgments

We are grateful to Edward Laws (Department of Neurosurgery, Brigham and Women’s Hospital, Boston) for his critical evaluation and linguistic revision of this manuscript. This project was supported by grants from the National Natural Science Foundation of China (30800347), from the Science and Technology Department of Zhejiang Province (2007C33028), from the Health Bureau of Zhejiang Province (2007A138), and from Wenzhou Science and Technology Bureau (H20070040).

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Authors and Affiliations

  1. Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical College, 325000, Wenzhou, China

    Zhe Bao Wu, Wei Ming Zheng, Zhi Peng Su, Yong Chen, Jin Sen Wu, Cheng De Wang, Chen Lin & Qi Chuan Zhuge

  2. Biomedical Engineering Center, Biomechanics and Medical Information Institute, Beijing University of Technology, 100022, Beijing, China

    Yan Jun Zeng

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  1. Zhe Bao Wu
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Correspondence to Qi Chuan Zhuge.

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Wu, Z.B., Zheng, W.M., Su, Z.P. et al. 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 (2010). https://doi.org/10.1007/s11060-009-0107-y

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  • DOI: https://doi.org/10.1007/s11060-009-0107-y

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