Effect of inducible FHIT and p53 expression in the Calu-1 lung cancer cell line

A. Cavazzoni, M. Galetti, C. Fumarola, R. R. Alfieri, L. Roz, F. Andriani, P. Carbognani, M. Rusca, G. Sozzi, P. G. Petronini

Research output: Contribution to journalArticle

Abstract

Loss of FHIT expression and p53 mutations are critical events in the early stages of lung carcinogenesis. The restoration of Fhit function in FHIT-negative cancer cells has been reported to cause tumour suppression by inhibition of cell proliferation and/or activation of apoptotic pathways. However, the studies designed to elucidate the biological role of Fhit and its potential interaction with p53 have produced conflicting results. We investigated here the effects of the simultaneous restoration of FHIT and p53 in Calu-1 cells by using a hormone-inducible gene expression system. We demonstrate that the restoration of FHIT expression reinforces the anti-proliferative effect associated with the simultaneous replacement of p53. Indeed, a more pronounced inhibition of cell proliferation associated with an earlier and higher induction of p21waf1 mRNA and protein expression was observed in Fhit/p53-expressing cells compared with cells expressing p53 alone. This effect was not due to Fhit-mediated up-regulation of p53 expression; in fact p53 protein was expressed at the same level in both FHIT-positive and FHIT-negative cell clones. Consistent with this result, Fhit did not affect the expression of MDM2, a protein known to interact directly with p53 and target p53 for proteolytic degradation, thus down-regulating its activity.

Original languageEnglish
Pages (from-to)69-81
Number of pages13
JournalCancer Letters
Volume246
Issue number1-2
DOIs
Publication statusPublished - Feb 8 2007

    Fingerprint

Keywords

  • FHIT
  • Inducible expression system
  • Lung cancer
  • p21
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Cavazzoni, A., Galetti, M., Fumarola, C., Alfieri, R. R., Roz, L., Andriani, F., Carbognani, P., Rusca, M., Sozzi, G., & Petronini, P. G. (2007). Effect of inducible FHIT and p53 expression in the Calu-1 lung cancer cell line. Cancer Letters, 246(1-2), 69-81. https://doi.org/10.1016/j.canlet.2006.01.033