mTOR promotes pituitary tumor development through activation of PTTG1

被引：42

作者：

Chen, R. ^{[1
]}

Duan, J. ^{[1
]}

Li, L. ^{[1
]}

Ma, Q. ^{[1
]}

Sun, Q. ^{[1
]}

Ma, J. ^{[1
]}

Li, C. ^{[1
]}

Zhou, X. ^{[1
]}

Chen, H. ^{[1
]}

Jing, Y. ^{[1
]}

Zhao, S. ^{[1
]}

Wu, X. ^{[2
]}

Zhang, H. ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch,State Key Lab Med Mol Biol, Sch Basic Med,Inst Basic Med Sci,Dept Physiol, Beijing, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Internal Med, Div Endocrinol, Beijing, Peoples R China

来源：

ONCOGENE | 2017年 / 36卷 / 07期

基金：

中国国家自然科学基金;

关键词：

TUBEROUS SCLEROSIS COMPLEX; TRANSFORMING GENE PTTG; PROLACTIN-SECRETING CELLS; RECEPTOR-DEFICIENT MICE; LACTOTROPH HYPERPLASIA; MAMMALIAN TARGET; SUPPRESSOR GENE; TRANSGENIC MICE; MOUSE MODEL; ADENOMAS;

D O I：

10.1038/onc.2016.264

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：979 / 988

页数：10

共 62 条

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