| First Author | Rozenberg J | Year | 2009 |
| Journal | Mol Cancer Res | Volume | 7 |
| Issue | 5 | Pages | 654-64 |
| PubMed ID | 19435810 | Mgi Jnum | J:205249 |
| Mgi Id | MGI:5544412 | Doi | 10.1158/1541-7786.MCR-08-0011 |
| Citation | Rozenberg J, et al. (2009) Inhibition of CREB function in mouse epidermis reduces papilloma formation. Mol Cancer Res 7(5):654-64 |
| abstractText | 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-Ras(Ha)-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. |
