Effects of exogenous p53 transduction in thyroid tumor cells with different p53 status

Recovery of p53 function in undifferentiated thyroid carcinoma cells carryi ng an altered p53 gene is able to modify cell tumorigenic properties. It is not known whether such an effect may also be achieved in thyroid cancer ce lls expressing wild-type p53, as in the majority of differentiated thyroid carcinomas. Effects of p53 transduction in a thyroid carcinoma cell line (F RO) exhibiting a wild-type endogenous p53 gene, in comparison to a cell lin e (WRO) exhibiting mutant p53, were investigated by using an inducible chim eric construct containing human p53 complementary DNA fused to the ligand b inding domain of the estrogen receptor (p53ER). FRO cells were unaffected b y exogenous p53 expression in terms of both proliferation and viability. On the contrary, p53 reexpression in WRO cells containing hemizygous mutated p53 allele caused a strong growth inhibition due to cell accumulation in th e G(1) phase of the cell cycle. In addition, exogenous p53 did not influenc e FRO cell behavior in response to TSH treatment or modify cell resistance to the chemotherapeutic agent, doxorubicin. Our results indicate that exoge nous expression of wild-type p53 affects thyroid tumorigenic properties onl y in cells carrying an altered p53, whereas it is ineffective in cells expr essing wild-type p53 activity. Therefore, the endogenous p53 status seems t o be a major determinant for the effectiveness of a p53-based gene therapy for thyroid cancer.