title: ESR1 and its antagonist fulvestrant in pituitary adenomas.
abstract: Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X2= 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs.
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China.
authors.forename: Yake
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Beijing Tiantan Hospital, Beijing 100050, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Shan
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: zyz2004520@yeah.net.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000236:Adenoma / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015331:Cohort Studies; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009570:Nitriles; C113580:U 0126; D000077267:Fulvestrant; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Apoptosis; Estrogen receptor alpha; Fulvestrant; MAPK pathway; Pituitary adenomas