title: Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior.
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 ERalphamRNA and ERbetamRNA 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.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical College, 325000 Wenzhou, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Wei Ming
authors.initials: WM
authors.lastname: Zheng
authors.forename: Zhi Peng
authors.initials: ZP
authors.lastname: Su
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jin Sen
authors.initials: JS
authors.lastname: Wu
authors.forename: Cheng De
authors.initials: CD
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Yan Jun
authors.initials: YJ
authors.lastname: Zeng
authors.forename: Qi Chuan
authors.initials: QC
authors.lastname: Zhuge
mesh_terms: D000328:Adult; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004724:Endoscopy / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D015175:Prolactinoma / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D006727:Hormone Antagonists; D020033:Protein Isoforms; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D011960:Receptors, Estrogen; D001971:Bromocriptine