HUMAN THYROID ANAPLASTIC CARCINOMA CELL PROLIFERATION AND DIFFERENTIATION ARE MODULATED BY RECOVERY OF P53 ACTIVITY.

Alterations of the tumour suppressor p53 protein are detected with high frequency in anaplastic thyroid carcinomas (ATC) while are very rare in differentiated thyroid neoplasm. They may therefore be responsible for the loss of differentiation and aggressive biological behaviour of ATC. Aim of this study has been to analyze the effect of restoration of p53 function on the proliferation and differentiation of human ATC cells (ARO), characterized by the presence of an altered p53. ARO cell clones have been stable transfected with a temperature-sensitive mutant p53 , which, at 32°C, exhibits wild type p53-like properties, but is inactive at 37°C. When grown at 32°C, cell clones expressing exogenous p53, showed a clear reduction of cell proliferation rate, which was proportional to p53 nuclear levels and characterised by a reduction of the number of cells entering the G2 phase of the cell cycle. At the permissive temperature, an increased expression of TSH receptor and thyroperoxidase mRNAs was also noted by semi-quantitative RT-PCR analysis, while experiments are in progress to evaluate the reappearance of TSh dependence, in terms of cAMP induction and 131I uptake stimulation. The likelihood of re-inducing follicular differentiation properties may lead to a more efficient treatment of ATC.