title: mTOR promotes pituitary tumor development through activation of PTTG1.
abstract: As one of the most common intracranial tumors, pituitary tumor is associated with high morbidity. Effective therapy is currently not available for some pituitary tumors due to the largely undefined pathological processes of pituitary tumorigenesis. In this study, hyperactivation of mammalian/mechanistic target of rapamycin (mTOR) signaling was observed in estrogen-induced rat pituitary tumor and mTOR inhibitor rapamycin blocked the tumor development. Pituitary knockout of either mTOR signaling pathway negative regulator Tsc1 or Pten caused mouse pituitary prolactinoma, which was abolished by rapamycin treatment. Mechanistically, the expression of pituitary tumor transforming gene 1 (PTTG1) was upregulated in an mTOR complex 1-dependent manner. Overexpressed PTTG1 was crucial in hyperactive mTOR-mediated tumorigenesis. mTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with mTOR hyperactivation.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D064249:Securin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: C578005:PTTG1 protein, mouse; D064249:Securin; C000624650:TSC1 protein, human; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse