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p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells.

Abstract

Alterations of the tumor suppressor gene p53 are uncommon in differentiated thyroid neoplasia but are detected at high frequency in anaplastic thyroid carcinoma suggesting that impaired p53 function may contribute to the undifferentiated and highly aggressive phenotype of these tumors. Effects of wild type p53 (wt-p53) re-expression were investigated in a human anaplastic thyroid carcinoma cell line (ARO) expressing a mutated p53. ARO cells were stably transfected with the temperature-sensitive p53 Val135 gene (ts-p53) which exhibits wild type-like activity at 32 degrees C. Exogenous wt-p53 function in ARO-tsp53 clones was assessed by evaluating its transcriptional activity on a CAT reporter vector containing p53 binding sites. At 32 degrees C, a significant reduction in the proliferation rate (approximately or equal to 50%) was observed, with accumulation of cells in the G0/G1 phase of the cell cycle. This effect was accompanied by induction of the expression of the growth inhibitor p21/Waf1 gene. At 32 degrees C, ARO-tsp53 clones also showed a marked impairment of their tumorigenic potential. Furthermore, transfected clones re-acquired the ability to respond to thyrotropin (TSH) stimulation showing an increased expression of thyroid-specific genes (thyroglobulin, thyroperoxidase and TSH receptor). In conclusion, re-expression of wt-p53 activity in ARO cells, inhibits cell proliferation and restores responsiveness to physiological stimuli.

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  • Authors+Show Affiliations

    ,

    Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome, Italy.

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    Source

    Oncogene 14:6 1997 Feb 13 pg 729-40

    MeSH

    Carcinoma
    Cell Differentiation
    Cell Division
    Cyclin-Dependent Kinase Inhibitor p21
    Cyclins
    Gene Expression
    Genes, p53
    Humans
    Mutation
    Phenotype
    Temperature
    Thyroid Neoplasms
    Transfection
    Tumor Cells, Cultured
    Tumor Suppressor Protein p53

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    9038381

    Citation

    Moretti, F, et al. "P53 Re-expression Inhibits Proliferation and Restores Differentiation of Human Thyroid Anaplastic Carcinoma Cells." Oncogene, vol. 14, no. 6, 1997, pp. 729-40.
    Moretti F, Farsetti A, Soddu S, et al. P53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene. 1997;14(6):729-40.
    Moretti, F., Farsetti, A., Soddu, S., Misiti, S., Crescenzi, M., Filetti, S., ... Pontecorvi, A. (1997). P53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene, 14(6), pp. 729-40.
    Moretti F, et al. P53 Re-expression Inhibits Proliferation and Restores Differentiation of Human Thyroid Anaplastic Carcinoma Cells. Oncogene. 1997 Feb 13;14(6):729-40. PubMed PMID: 9038381.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. AU - Moretti,F, AU - Farsetti,A, AU - Soddu,S, AU - Misiti,S, AU - Crescenzi,M, AU - Filetti,S, AU - Andreoli,M, AU - Sacchi,A, AU - Pontecorvi,A, PY - 1997/2/13/pubmed PY - 1997/2/13/medline PY - 1997/2/13/entrez SP - 729 EP - 40 JF - Oncogene JO - Oncogene VL - 14 IS - 6 N2 - Alterations of the tumor suppressor gene p53 are uncommon in differentiated thyroid neoplasia but are detected at high frequency in anaplastic thyroid carcinoma suggesting that impaired p53 function may contribute to the undifferentiated and highly aggressive phenotype of these tumors. Effects of wild type p53 (wt-p53) re-expression were investigated in a human anaplastic thyroid carcinoma cell line (ARO) expressing a mutated p53. ARO cells were stably transfected with the temperature-sensitive p53 Val135 gene (ts-p53) which exhibits wild type-like activity at 32 degrees C. Exogenous wt-p53 function in ARO-tsp53 clones was assessed by evaluating its transcriptional activity on a CAT reporter vector containing p53 binding sites. At 32 degrees C, a significant reduction in the proliferation rate (approximately or equal to 50%) was observed, with accumulation of cells in the G0/G1 phase of the cell cycle. This effect was accompanied by induction of the expression of the growth inhibitor p21/Waf1 gene. At 32 degrees C, ARO-tsp53 clones also showed a marked impairment of their tumorigenic potential. Furthermore, transfected clones re-acquired the ability to respond to thyrotropin (TSH) stimulation showing an increased expression of thyroid-specific genes (thyroglobulin, thyroperoxidase and TSH receptor). In conclusion, re-expression of wt-p53 activity in ARO cells, inhibits cell proliferation and restores responsiveness to physiological stimuli. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/9038381/p53_re_expression_inhibits_proliferation_and_restores_differentiation_of_human_thyroid_anaplastic_carcinoma_cells_ L2 - http://dx.doi.org/10.1038/sj.onc.1200887 DB - PRIME DP - Unbound Medicine ER -