title: Genes differentially expressed in prolactinomas responsive and resistant to dopamine agonists.
abstract: OBJECTIVE
  Prolactin (PRL) secretion and its gene expression are inhibited by dopamine. Prolactinomas are the most common secreting pituitary adenomas, and dopamine agonists (DA) are the first choice for their treatment. However, a subset of patients is resistant to DA. As the mechanisms involved in DA resistance are not fully understood, the aim of this study was to obtain new insights regarding the molecular differences between the prolactinomas that are responsive to DA and those that are resistant.
  
  
  METHODS
  Tumor tissue samples were collected from 17 patients who harbored prolactinomas, which were classified as responsive or resistant according to their clinical and laboratorial reaction to DA. The expression of 6 genes was evaluated by real-time polymerase chain reaction: dopamine receptor type 2 (DRD(2)), nerve growth factor-beta (NGFB) and its receptor (NGFR), estrogen receptor-alpha (ERA), estrogen receptor-beta (ERB) and the pituitary tumor transforming gene (PTTG).
  
  
  RESULTS
  Median DRD(2) and NGFR expression in responsive patients was significantly higher than in resistant ones (p = 0.029 and p = 0.020, respectively). Moreover, the expressions of DRD(2) and NGFR were positively correlated with PRL decrease during treatment (r = 0.66, p = 0.005 and r = 0.57, p = 0.044, respectively). Furthermore, ERB expression was positively correlated to PTTG expression (r = 0.68, p = 0.032) and negatively correlated to NGFB expression (r = -0.75, p = 0.02).
  
  
  CONCLUSIONS
  DRD(2) and NGFR expressions are related to the responsiveness of prolactinoma to DA. However, PTTG, ERB and ERA expressions are not. Also ERB, ERA and PTTG expressions did not present a clear correlation to tumor aggressiveness. Furthermore, the response of prolactinomas to DA should be viewed as a spectrum ranging from the most responsive to the most resistant ones.
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. vanessa@endo.med.br
authors.forename: Vanessa Q
authors.initials: VQ
authors.lastname: Passos
authors.forename: Maria Angela H Z
authors.initials: MA
authors.lastname: Fortes
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
authors.forename: Marcello D
authors.initials: MD
authors.lastname: Bronstein
mesh_terms: D000328:Adult; D018491:Dopamine Agonists / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D012333:RNA, Messenger