REEXPRESSION OF THYROID PEROXIDASE IN A DERIVATIVE OF AN UNDIFFERENTIATED THYROID-CARCINOMA CELL-LINE BY INTRODUCTION OF WILD-TYPE P53

Loss of function of p53 is believed to result in transformation throug h impairment of its properties as a transcription factor, which interf eres with the regulation of the cell cycle and under certain condition s, with programmed cell death. We report that stable transfection of c lonal undifferentiated thyroid carcinoma cell lines harboring endogeno us p53 mutations with a wild-type p53 expression vector only rarely yi elds transfectants expressing authentic wild-type p53. Among these, mo st exhibited an increase in doubling time and an impairment of colony formation in soft agar. Only one clonal wild-type p53-overexpressing d erivative of the NPA papillary carcinoma cell line was obtained, and t hese cells were found to reexpress thyroid peroxidase (TPO). This clon e also demonstrated reexpression of the paired box domain transcriptio n factor Pax-8, which specifically activates transcription of TPO. Wil d-type p53 did not directly stimulate transcriptional activity of a TP O promoter construct. Although the low frequency of authentic wild-typ e p53 stable transfectants limits the power of this analysis, these da ta suggest that in addition to its role in malignant transformation, p 53 may be significant in the determination or maintenance of cell diff erentiation in thyroid neoplasms.