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mTOR promotes pituitary tumor development through activation of PTTG1

R Chen1, J Duan1, L Li1

  • 1State 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.

Oncogene
|August 16, 2016
PubMed

Insights

Hyperactivation of the mammalian target of rapamycin (mTOR) pathway drives pituitary tumor growth. Inhibiting mTOR with rapamycin blocked tumor development, revealing a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Pituitary tumors are common intracranial neoplasms with significant morbidity.
  • Current effective therapies are limited due to poorly understood tumorigenesis.
  • Mammalian target of rapamycin (mTOR) signaling is implicated in various cancers.

Purpose of the Study:

  • To investigate the role of mTOR signaling in pituitary tumorigenesis.
  • To explore the therapeutic potential of mTOR inhibitors in pituitary tumors.
  • To elucidate the molecular mechanisms underlying mTOR-driven pituitary tumor formation.

Main Methods:

  • Estrogen-induced rat pituitary tumor model.
  • Genetic knockout of mTOR pathway regulators (Tsc1, Pten) in mouse pituitary.
  • Administration of mTOR inhibitor rapamycin.
  • Analysis of pituitary tumor transforming gene 1 (PTTG1) expression.

Main Results:

  • Hyperactivation of mTOR signaling was observed in estrogen-induced rat pituitary tumors.
  • Rapamycin treatment blocked tumor development in rats.
  • Knockout of Tsc1 or Pten in mouse pituitary caused prolactinoma, which was reversed by rapamycin.
  • PTTG1 expression was upregulated in an mTOR complex 1-dependent manner.
  • Overexpressed PTTG1 was critical for mTOR-mediated pituitary tumorigenesis.

Conclusions:

  • The mTOR-PTTG1 signaling axis is a key driver of pituitary tumorigenesis.
  • Targeting the mTOR pathway, particularly the mTOR-PTTG1 axis, shows therapeutic promise for pituitary tumors with mTOR hyperactivation.

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