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 language | English (US) |
|---|---|
| Pages (from-to) | 654-664 |
| Number of pages | 11 |
| Journal | Molecular Cancer Research |
| Volume | 7 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2009 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Oncology
- Cancer Research
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Inhibition of CREB function in mouse epidermis reduces papilloma formation. / Rozenberg, Julian; Rishi, Vikas; Orosz, Andras; Moitra, Jaideep; Glick, Adam; Vinson, Charles.
In: Molecular Cancer Research, Vol. 7, No. 5, 01.05.2009, p. 654-664.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition of CREB function in mouse epidermis reduces papilloma formation
AU - Rozenberg, Julian
AU - Rishi, Vikas
AU - Orosz, Andras
AU - Moitra, Jaideep
AU - Glick, Adam
AU - Vinson, Charles
PY - 2009/5/1
Y1 - 2009/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=66349111223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66349111223&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-08-0011
DO - 10.1158/1541-7786.MCR-08-0011
M3 - Article
C2 - 19435810
AN - SCOPUS:66349111223
VL - 7
SP - 654
EP - 664
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 5
ER -