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Reexpression of Thyroid Peroxidase in a Derivative of an Undifferentiated Thyroid Carcinoma Cell Line by Introduction of Wild-Type p53¹

Division of Endocrinology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, California 90048 [J. A. F., S-H. T., K. Z., R. G.]; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy [R. D. L.]; and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facolta' di Medicina e Chirurgia, Via Pansini 5, 80311 Naples, Italy [A. F.]

Loss of function of p53 is believed to result in transformation through impairment of its properties as a transcription factor, which interferes with the regulation of the cell cycle and under certain conditions, with programmed cell death. We report that stable transfection of clonal undifferentiated thyroid carcinoma cell lines harboring endogenous p53 mutations with a wild-type p53 expression vector only rarely yields transfectants expressing authentic wild-type p53. Among these, most exhibited an increase in doubling time and an impairment of colony formation in soft agar. Only one clonal wild-type p53-overexpressing derivative of the NPA papillary carcinoma cell line was obtained, and these cells were found to reexpress thyroid peroxidase (TPO). This clone also demonstrated reexpression of the paired box domain transcription factor Pax-8, which specifically activates transcription of TPO. Wild-type p53 did not directly stimulate transcriptional activity of a TPO promoter construct. Although the low frequency of authentic wild-type p53 stable transfectants limits the power of this analysis, these data suggest that in addition to its role in malignant transformation, p53 may be significant in the determination or maintenance of cell differentiation in thyroid neoplasms.

¹ This work was supported by NIH Grants CA50706 and DK42792 and by a grant from the Herbert family.

² To whom requests for reprints should be addressed, at University of Cincinnati Medical Center, Division of Endocrinology and Metabolism, 231 Bethesda Avenue, Room 5564, Cincinnati, OH 45267-0547. Phone: (513) 558-4444; Fax: (513) 558-8581.

Received 8/10/95. Accepted 12/12/95.

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