Mammalian target of rapamycin is the key effector of phosphatidylinositol- 3-OH-initiated proliferative signals in the thyroid follicular epithelium

Nicole Yeager, Charlene Brewer, Kathy Qi Cai, Xiangxi Xu, Antonio Di Cristofano

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling cascade is becoming increasingly recognized as a common feature of thyroid follicular neoplasms. We have recently shown that conditional loss of Pten in the mouse thyroid follicular cells is sufficient to stimulate continuous autonomous growth, leading to a homogeneously hyperplastic gland and to the development of follicular adenomas. Because the PI3K/AKT cascade can activate a plethora of different signaling pathways, it is still unclear which of these may represent the key mitogenic output of PI3K-initiated signaling. Here, we show that the in vivo proliferative response to chronic PI3K activation profoundly relies on the activation of the mammalian target of rapamycin (mTOR)/S6K1 axis, and that mTOR inhibition in Pten mutant mice and cells restores virtually normal proliferation rates, despite the presence of still elevated Akt activity, at least in part by down-regulating cyclins D1 and D3, and without affecting cell survival.

Original languageEnglish
Pages (from-to)444-449
Number of pages6
JournalCancer Research
Volume68
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

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Sirolimus
Phosphatidylinositols
Phosphatidylinositol 3-Kinases
Thyroid Gland
Epithelium
Cyclin D3
Cyclin D1
Thyroid Neoplasms
Adenoma
Cell Survival
hydroxide ion
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mammalian target of rapamycin is the key effector of phosphatidylinositol- 3-OH-initiated proliferative signals in the thyroid follicular epithelium. / Yeager, Nicole; Brewer, Charlene; Cai, Kathy Qi; Xu, Xiangxi; Di Cristofano, Antonio.

In: Cancer Research, Vol. 68, No. 2, 15.01.2008, p. 444-449.

Research output: Contribution to journalArticle

Yeager, Nicole ; Brewer, Charlene ; Cai, Kathy Qi ; Xu, Xiangxi ; Di Cristofano, Antonio. / Mammalian target of rapamycin is the key effector of phosphatidylinositol- 3-OH-initiated proliferative signals in the thyroid follicular epithelium. In: Cancer Research. 2008 ; Vol. 68, No. 2. pp. 444-449.
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