Inhibition of CREB function in mouse epidermis reduces papilloma formation

Julian Rozenberg, Vikas Rishi, Andras Orosz, Jaideep Moitra, Adam Glick, Charles Vinson

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We used a double transgenic tetracycline system to conditionally express A-CREB, a dominant negative protein that prevents the DNA binding and function of cAMP-responsive element binding protein (CREB) family members, in mouse basal epidermis using the keratin 5 promoter. There was no phenotype in the adult. However, following a 7,12-dimethylbenz(a)anthracene (DMBA)/phorbol-12-myristate- 13-acetate two-stage skin carcinogenesis experiment, A-CREB - expressing epidermis develop 5-fold fewer papillomas than wild-type controls. However, A-CREB expression one month after DMBA treatment does not prevent papilloma formation, suggesting that CREB functions at an early stage of papilloma formation. Oncogenic H-Ras genes with A→T mutations in codon 61 were found in wild-type skin but not in A-CREB - expressing skin 2 days after DMBA treatment, suggesting that A-CREB either prevents DMBA mutagenesis or kills oncogenic H-Ras cells. In primary keratinocyte cultures, A-CREB expression induced apoptosis of v-RasHa-infected cells and suppressed the expression of cell cycle proteins cyclin B1 and cyclin D1. These results suggest that inhibiting CREB function is a valuable cancer prevention strategy.

Original languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalMolecular Cancer Research
Volume7
Issue number5
DOIs
StatePublished - May 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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