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

Alfredo Pontecorvi, Fabiola Moretti, Antonella Farsetti, Silvia Soddu, Silvia Misiti, Marco Crescenzi, Sebastiano Filetti, Mario Andreoli, Ada Sacchi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

127 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)729-740
Numero di pagine12
RivistaOncogene
Volume14
DOI
Stato di pubblicazionePubblicato - 1997

Keywords

  • 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

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