PMID- 18997818
OWN - NLM
STAT- MEDLINE
DCOM- 20090217
LR  - 20220408
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 28
IP  - 4
DP  - 2009 Jan 29
TI  - PTEN deficiency accelerates tumour progression in a mouse model of thyroid 
      cancer.
PG  - 509-17
LID - 10.1038/onc.2008.407 [doi]
AB  - Inactivation and silencing of PTEN have been observed in multiple cancers, 
      including follicular thyroid carcinoma. PTEN (phosphatase and tensin homologue 
      deleted from chromosome 10) functions as a tumour suppressor by opposing the 
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. 
      Despite correlative data, how deregulated PTEN signalling leads to thyroid 
      carcinogenesis is not known. Mice harbouring a dominant-negative mutant thyroid 
      hormone receptor beta (TRbeta(PV/PV) mice) spontaneously develop follicular 
      thyroid carcinoma and distant metastases similar to human cancer. To elucidate 
      the role of PTEN in thyroid carcinogenesis, we generated TRbeta(PV/PV) mice 
      haploinsufficient for Pten (TRbeta(PV/PV)Pten(+/-) mouse). PTEN deficiency 
      accelerated the progression of thyroid tumour and increased the occurrence of 
      metastasis spread to the lung in TRbeta(PV/PV)Pten(+/-) mice, thereby 
      significantly reducing their survival as compared with TRbeta(PV/PV)Pten(+/+) 
      mice. AKT activation was further increased by two-fold in TRbeta(PV/PV)Pten(+/-) 
      mice thyroids, leading to increased activity of the downstream mammalian target 
      of rapamycin (mTOR)-p70S6K signalling and decreased activity of the forkhead 
      family member FOXO3a. Consistently, cyclin D1 expression was increased. Apoptosis 
      was decreased as indicated by increased expression of nuclear factor-kappaB 
      (NF-kappaB) and decreased caspase-3 activity in the thyroids of 
      TRbeta(PV/PV)Pten(+/-) mice. Our results indicate that PTEN deficiency resulted 
      in increased cell proliferation and survival in the thyroids of 
      TRbeta(PV/PV)Pten(+/-) mice. Altogether, our study provides direct evidence to 
      indicate that in vivo, PTEN is a critical regulator in the follicular thyroid 
      cancer progression and invasiveness.
FAU - Guigon, C J
AU  - Guigon CJ
AD  - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer 
      Institute, Bethesda, MD, USA.
FAU - Zhao, L
AU  - Zhao L
FAU - Willingham, M C
AU  - Willingham MC
FAU - Cheng, S-Y
AU  - Cheng SY
LA  - eng
GR  - ZIA BC011191-03/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20081110
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carrier Proteins)
RN  - 0 (Ccnd1 protein, mouse)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (FoxO3 protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Thyroid Hormone Receptors beta)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
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  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Carrier Proteins/genetics/metabolism
MH  - Caspase 3/genetics/metabolism
MH  - Cell Proliferation
MH  - Cell Survival/genetics
MH  - Chromosomes, Mammalian/genetics/metabolism
MH  - Cyclin D1/genetics/metabolism
MH  - Disease Models, Animal
MH  - Enzyme Activation/genetics
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - Lung Neoplasms/genetics/*metabolism/pathology/secondary
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - NF-kappa B/genetics/metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - PTEN Phosphohydrolase/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - *Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases
MH  - Thyroid Hormone Receptors beta/genetics/metabolism
MH  - Thyroid Neoplasms/genetics/*metabolism/pathology
PMC - PMC3457778
MID - NIHMS405492
EDAT- 2008/11/11 09:00
MHDA- 2009/02/20 09:00
PMCR- 2012/09/25
CRDT- 2008/11/11 09:00
PHST- 2008/11/11 09:00 [pubmed]
PHST- 2009/02/20 09:00 [medline]
PHST- 2008/11/11 09:00 [entrez]
PHST- 2012/09/25 00:00 [pmc-release]
AID - onc2008407 [pii]
AID - 10.1038/onc.2008.407 [doi]
PST - ppublish
SO  - Oncogene. 2009 Jan 29;28(4):509-17. doi: 10.1038/onc.2008.407. Epub 2008 Nov 10.