Transient ectopic expression of PTEN in thyroid cancer cell lines induces cell cycle arrest and cell type-dependent cell death

The tumour suppressor gene PTEN/MMAC1/TEP1 has been implicated in a variety of human cancers and several inherited hamartoma tumour syndromes, includi ng 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 PTENs growth-suppressive effects on thyroid. We found that 1 of 10 thyroid cance r lines [follicular thyroid carcinoma FTC-133] had hemizygous deletion and a splice variant IVS4-19G-->A in the remaining allele, Four lines, includin g 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 tra nscript and relatively high levels of PTEN protein. Transient expression of PTEN in seven thyroid cancer cell lines resulted in G(1) arrest in two wel l differentiated papillary thyroid cancer lines (PTCs) and both G(1), arres t and cell death in the remaining five lines, including three FTCs, one poo rly differentiated PTC and one undifferentiated thyroid cancer. The level o f 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 PTENinactivation in thyroid cancer and PT EN exerts its tumour-suppressive effect on thyroid cancer through the inhib ition of cell cycle progression alone or both cell cycle progression and ce ll death.