@article{thompson_zhu_hall_house_ranjan_burr_he_owens_smart_2011, title={C/EBP alpha Expression Is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBP alpha Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas}, volume={131}, ISSN={["0022-202X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79956039252&partnerID=MN8TOARS}, DOI={10.1038/jid.2011.31}, abstractNote={Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G<sub>1</sub> checkpoint, and diminished or ablated expression of C/EBPα results in G<sub>1</sub> checkpoint failure. In the current study we observed that C/EBPα 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/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure <i>in vivo</i> in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.}, number={6}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Thompson, Elizabeth A. and Zhu, Songyun and Hall, Jonathan R. and House, John S. and Ranjan, Rakesh and Burr, Jeanne A. and He, Yu-Ying and Owens, David M. and Smart, Robert C.}, year={2011}, month={Jun}, pages={1339–1346} }
 @article{house_zhu_ranjan_linder_smart_2010, title={C/EBP alpha and C/EBP beta Are Required for Sebocyte Differentiation and Stratified Squamous Differentiation in Adult Mouse Skin}, volume={5}, ISSN={["1932-6203"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952118221&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0009837}, abstractNote={C/EBPα and C/EBPβ are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPα and C/EBPβ in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPα or C/EBPβ alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPα and C/EBPβ in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPα and C/EBPβ in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPα and C/EBPβ are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.}, number={3}, journal={PLOS ONE}, author={House, John S. and Zhu, Songyun and Ranjan, Rakesh and Linder, Keith and Smart, Robert C.}, year={2010}, month={Mar} }
 @article{ranjan_thompson_yoon_smart_2009, title={C/EBP alpha expression is partially regulated by C/EBP beta in response to DNA damage and C/EBP alpha-deficient fibroblasts display an impaired G(1) checkpoint}, volume={28}, ISSN={["1476-5594"]}, DOI={10.1038/onc.2009.176}, abstractNote={We observed that CCAAT/enhancer-binding protein (C/EBP)alpha is highly inducible in primary fibroblasts by DNA-damaging agents that induce strand breaks, alkylate and crosslink DNA as well as those that produce bulky DNA lesions. Fibroblasts deficient in C/EBPalpha (C/EBPalpha(-/-)) display an impaired G1 checkpoint as evidenced by an inappropriate entry into the S-phase in response to DNA damage, and these cells also display an enhanced G1/S transition in response to mitogens. The induction of C/EBPalpha by DNA damage in fibroblasts does not require p53. Electrophoretic mobility shift assay (EMSA) analysis of nuclear extracts prepared from ultraviolet B (UVB)- and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated fibroblasts showed increased binding of C/EBPbeta to a C/EBP consensus sequence and chromatin immunoprecipitation (ChIP) analysis also showed increased C/EBPbeta binding to the C/EBPalpha promoter. To determine whether C/EBPbeta has a function in the regulation of C/EBPalpha, we treated C/EBPbeta(-/-) fibroblasts with UVB or MNNG. We observed that C/EBPalpha induction was impaired in both UVB- and MNNG-treated C/EBPbeta(-/-) fibroblasts. Our study shows a novel function for C/EBPbeta in the regulation of C/EBPalpha in response to DNA damage and provides definitive genetic evidence that C/EBPalpha has a critical role in the DNA damage G1 checkpoint.}, number={36}, journal={ONCOGENE}, author={Ranjan, R. and Thompson, E. A. and Yoon, K. and Smart, R. C.}, year={2009}, month={Sep}, pages={3235–3245} }