) Basal Cell Carcinomas (BCCs) are the commonest human cancer and are of increasing incidence, due in part to increased recreational sunlight exposure. During the past two years, the fundamental molecular defect apparently underlying the aberrant behavior of these tumor cells has been uncovered; all BCCs have abnormal regulation of the hedgehog signaling pathway. Patients with the basal cell nevus syndrome (BCNS) are susceptible to developing multiple basal cell carcinomas because they inherit one defective allele of the PTC gene, which encodes a protein that hampers hedgehog signaling. Mice hemizygous for a functioning ptc gene, like BCNS patients with the same genotype, are highly susceptible to the development of BCCs, and these are induced by the relevant environmental insult-ultraviolet light. This project will utilize the growing knowledge of HCC signaling aberrations, the murine BCC model, and the chemopreventive effects of tea extracts to develop agents efficacious in preventing BCC carcinogenesis in mice and man and will investigate the mechanisms underlying such efficacy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZCA1-SRRB-Y (J3))
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Kopelovich, Levy
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Tang, Jean Y; Xiao, Tony Zheng; Oda, Yuko et al. (2011) Vitamin D3 inhibits hedgehog signaling and proliferation in murine Basal cell carcinomas. Cancer Prev Res (Phila) 4:744-51
Davari, Parastoo; Hebert, Jennifer L; Albertson, Donna G et al. (2010) Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1+/- mice. Carcinogenesis 31:968-73
Tang, Jean Y; Wu, Angela; Linos, Eleni et al. (2010) High prevalence of vitamin D deficiency in patients with basal cell nevus syndrome. Arch Dermatol 146:1105-10
Tang, Jean Y; Aszterbaum, Michelle; Athar, Mohammad et al. (2010) Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in genetically predisposed PTCH1+/- humans and mice. Cancer Prev Res (Phila) 3:25-34
So, Po-Lin; Fujimoto, Michele A; Epstein Jr, Ervin H (2008) Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis. Mol Cancer Ther 7:1275-84
Athar, Mohammad; Tang, Xiuwei; Lee, Juliette L et al. (2006) Hedgehog signalling in skin development and cancer. Exp Dermatol 15:667-77
Bickers, David R; Athar, Mohammad (2006) Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol 126:2565-75
So, Po-Lin; Langston, Alexander W; Daniallinia, Nancy et al. (2006) Long-term establishment, characterization and manipulation of cell lines from mouse basal cell carcinoma tumors. Exp Dermatol 15:742-50
Lee, Juliette Lois; Kim, Arianna; Kopelovich, Levy et al. (2005) Differential expression of E prostanoid receptors in murine and human non-melanoma skin cancer. J Invest Dermatol 125:818-25
Vogt, Annika; Hebert, Jennifer; Hwang, Jimmy et al. (2005) Anti-rejection drug treatment increases basal cell carcinoma burden in Ptch1+/- mice. J Invest Dermatol 124:263-7

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