| First Author | Thompson EA | Year | 2011 |
| Journal | J Invest Dermatol | Volume | 131 |
| Issue | 6 | Pages | 1339-46 |
| PubMed ID | 21346772 | Mgi Jnum | J:182080 |
| Mgi Id | MGI:5314692 | Doi | 10.1038/jid.2011.31 |
| Citation | Thompson EA, et al. (2011) C/EBPalpha expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPalpha confers susceptibility to UVB-induced skin squamous cell carcinomas. J Invest Dermatol 131(6):1339-46 |
| abstractText | Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPalpha (CCAAT/enhancer-binding protein-alpha) in the DNA damage response network, where C/EBPalpha is induced following UVB DNA damage, regulates the G(1) checkpoint, and diminished or ablated expression of C/EBPalpha results in G(1) checkpoint failure. In the current study we observed that C/EBPalpha is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPalpha expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPalpha similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPalpha. To determine the significance of C/EBPalpha in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPalpha (CKOalpha) were exposed to UVB. CKOalpha mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOalpha mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPalpha is silenced in human SCC and loss of C/EBPalpha confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB. |
