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mTOR promotes pituitary tumor development through activation of PTTG1

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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.

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Acknowledgements

We thank the staff of Animal Center, and Department of Pathology, Peking Union Medical College (Beijing, China) for help with in vivo studies and instructions on pathological analysis. This work was supported by the National Basic Research Program of China (973 Program) (2015CB553802), the National Natural Science Foundation of China (81372861, 30788004), and the Ministry of Education of China (111 project: B08007).

Author contributions

RC and HZ designed experiments, analyzed results and supervised the project. RC, JD, LL, XZ and SZ performed the in vivo experiments, image processing and histological quantification. RC, QM, QS, JM, CL, XZ, HC and YJ performed in vitro experiments. RC and HZ wrote the manuscript with XW provided medical advice.

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Authors and Affiliations

  1. Department of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    R Chen, J Duan, L Li, Q Ma, Q Sun, J Ma, C Li, X Zhou, H Chen, Y Jing, S Zhao & H Zhang

  2. Division of Endocrinology, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

    X Wu

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  1. R Chen
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Chen, R., Duan, J., Li, L. et al. mTOR promotes pituitary tumor development through activation of PTTG1. Oncogene 36, 979–988 (2017). https://doi.org/10.1038/onc.2016.264

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