Title: C/EBPýý expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPýý confers susceptibility to UVB-induced skin squamous cell carcinomas.

Authors: Thompson, Elizabeth A; Zhu, Songyun; Hall, Jonathan R; House, John S; Ranjan, Rakesh; Burr, Jeanne A; He, Yu-Ying; Owens, David M; Smart, Robert C

Published In J Invest Dermatol, (2011 Jun)

Abstract: Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPýý (CCAAT/enhancer-binding protein-ýý) in the DNA damage response network, where C/EBPýý is induced following UVB DNA damage, regulates the G(1) checkpoint, and diminished or ablated expression of C/EBPýý results in G(1) checkpoint failure. In the current study we observed that C/EBPýý 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/EBPýý expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPýý similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPýý. To determine the significance of C/EBPýý in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPýý (CKOýý) were exposed to UVB. CKOýý mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOýý 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/EBPýý is silenced in human SCC and loss of C/EBPýý confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.

PubMed ID: 21346772

MeSH Terms: No MeSH terms associated with this publication