Suppression of Ras-mediated NIH3T3 transformation by p19(ARF) does not involve alterations of cell growth properties

Viola Calabrò, Tiziana Parisi, Antonio Di Cristofano, Girolama La Mantia

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The INK4a gene, one of the most frequently disrupted loci in human cancer, encodes two unrelated proteins, p16(INK4a) and p19(ARF), that both block cell proliferation, p16(INK4a) is a component of the Rb regulatory pathway, while p19(ARF) has been functionally related to p53. Moreover, p16(INK4a) is inactivated in many human tumors, while it has been very recently reported that p19(ARF) null mice develop tumors early in life. We show here that p19(ARF) is able to inhibit the formation of G418-resistant colonies when transfected into human and mouse cell lines expressing wild-type p53, regardless of p16 status. Moreover its amino terminal domain encoded by exon 1β is still sufficient to obtain the same effect. We have analysed the ability of p19(ARF) to interfere with Ras-mediated cellular transformation in the NIH3T3 cell line. Cotransfection of p19(ARF) together with activated ras potently inhibited the formation of transformed foci in a dose-dependent manner. We have also isolated stable NIH3T3 transfectants expressing p19(ARF) and we have measured their growth properties as well as their efficiency of transformation by activated ras. Our results suggest that p19(ARF) can interfere with oncogene-mediated transformation, without significantly affecting NIH3T3 cell growth, at least at the levels of expression achieved in these experiments.

Original languageEnglish (US)
Pages (from-to)2157-2162
Number of pages6
Issue number12
StatePublished - Mar 25 1999
Externally publishedYes


  • Cell cycle regulation
  • Cellular transformation
  • INK4a locus
  • Tumor suppressor genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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