Transient ectopic expression of PTEN in thyroid cancer cell lines induces cell cycle arrest and cell type-dependent cell death. Hum Mol Genet 2001 Feb 01;10(3):251-8
Date
02/13/2001Pubmed ID
11159944DOI
10.1093/hmg/10.3.251Scopus ID
2-s2.0-0035253503 (requires institutional sign-in at Scopus site) 82 CitationsAbstract
The tumour suppressor gene PTEN/MMAC1/TEP1 has been implicated in a variety of human cancers and several inherited hamartoma tumour syndromes, including Cowden syndrome, which has a high risk of breast and thyroid cancer. We have previously reported that overexpression of PTEN in MCF-7 breast cancer cells induces cell cycle arrest and apoptosis. In this study, we analysed PTEN status at both the structural and expression levels and explored PTEN's growth-suppressive effects on thyroid. We found that 1 of 10 thyroid cancer lines [follicular thyroid carcinoma FTC-133] had hemizygous deletion and a splice variant IVS4--19G-->A in the remaining allele. Four lines, including FTC-133, express PTEN mRNA at low levels. In general, PTEN protein levels correlated with mRNA levels, except for NPA87, which has low levels of transcript and relatively high levels of PTEN protein. Transient expression of PTEN in seven thyroid cancer cell lines resulted in G(1) arrest in two well differentiated papillary thyroid cancer lines (PTCs) and both G(1) arrest and cell death in the remaining five lines, including three FTCs, one poorly differentiated PTC and one undifferentiated thyroid cancer. The level of phosphorylated Akt was inversely correlated with the endogenous level of PTEN protein and overexpression of PTEN-blocked Akt phosphorylation in all cells analysed. Our results suggest that downregulation of PTEN expression at the mRNA level plays a role in PTEN inactivation in thyroid cancer and PTEN exerts its tumour-suppressive effect on thyroid cancer through the inhibition of cell cycle progression alone or both cell cycle progression and cell death.
Author List
Weng LP, Gimm O, Kum JB, Smith WM, Zhou XP, Wynford-Thomas D, Leone G, Eng CAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenocarcinoma, FollicularApoptosis
Carcinoma, Papillary
Cell Cycle
Cell Death
Cell Division
DNA, Recombinant
G1 Phase
Gene Expression
Humans
Mutation
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases
Phosphorylation
Plasmids
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Thyroid Neoplasms
Transfection
Tumor Cells, Cultured
Tumor Suppressor Proteins