PMID- 18199538
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20211203
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 68
IP  - 2
DP  - 2008 Jan 15
TI  - Mammalian target of rapamycin is the key effector of 
      phosphatidylinositol-3-OH-initiated proliferative signals in the thyroid 
      follicular epithelium.
PG  - 444-9
LID - 10.1158/0008-5472.CAN-07-3030 [doi]
AB  - 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.
FAU - Yeager, Nicole
AU  - Yeager N
AD  - Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 
      19111, USA.
FAU - Brewer, Charlene
AU  - Brewer C
FAU - Cai, Kathy Qi
AU  - Cai KQ
FAU - Xu, Xiang-Xi
AU  - Xu XX
FAU - Di Cristofano, Antonio
AU  - Di Cristofano A
LA  - eng
GR  - CA97097/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenocarcinoma, Follicular/pathology
MH  - Animals
MH  - *Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Epithelium/metabolism/*physiology
MH  - Everolimus
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - PTEN Phosphohydrolase/genetics
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Kinases/metabolism/*physiology
MH  - Signal Transduction/physiology
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Thyroid Gland/metabolism/*physiology
MH  - Thyroid Neoplasms/pathology
EDAT- 2008/01/18 09:00
MHDA- 2008/02/15 09:00
CRDT- 2008/01/18 09:00
PHST- 2008/01/18 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2008/01/18 09:00 [entrez]
AID - 68/2/444 [pii]
AID - 10.1158/0008-5472.CAN-07-3030 [doi]
PST - ppublish
SO  - Cancer Res. 2008 Jan 15;68(2):444-9. doi: 10.1158/0008-5472.CAN-07-3030.