title: Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.
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.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Chuzhong
authors.initials: C
authors.lastname: Li
authors.forename: Jiwei
authors.initials: J
authors.lastname: Bai
authors.forename: Runchun
authors.initials: R
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Yongtu
authors.initials: Y
authors.lastname: Wu
authors.forename: Lichuan
authors.initials: L
authors.lastname: Hong
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Lan
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009077:Mucins; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced; D010911:Pituitary Neoplasms / Q000188:drug therapy*; D015175:Prolactinoma / Q000188:drug therapy*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D055273:Salivary Proline-Rich Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D005136:Eye Proteins; C466100:MUCL3 protein, human; D009077:Mucins; C524762:PRB3 protein, human; D011506:Proteins; D012333:RNA, Messenger; C474032:RP1L1 protein, human; D055273:Salivary Proline-Rich Proteins; D001971:Bromocriptine