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 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.
Fagin
J A
JA
Division of Endocrinology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine 90048, USA.
Tang
S H
SH
Zeki
K
K
Di Lauro
R
R
Fusco
A
A
Gonsky
R
R
D001483:Base Sequence; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D007453:Iodide Peroxidase; D008156:Luciferases