This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cutaneous basal cell (BCC) and squamous cell carcinoma (SCC) are the two most common cancers in the U.S.. While they both arise from the epidermis, these cancers differ dramatically in biological behavior and their underlying gene expression patterns have not been compared. We thus examined mRNA transcript levels in these malignancies as well as in psoriasis, a benign epidermal hyperplasia. Transcript expression patterns distinguish these disorders and identify differentially expressed genes. Among these is Egr-1, whose epidermal expression is consistently decreased in BCC and SCC but is elevated in psoriasis. Our preliminary data indicated that Egr-1 inhibits accelerated growth of benign and malignant epidermal cells in association with suppression of Cdc25A expression. We would like to confirm this finding and further investigate whether the phosphorylation status and kinase activity of Cdk2, a downstream target of Cdc25A, are affected. We hypothesize that gene expression profiling can differentiate epidermal hyperproliferative diseases and identify a role for Egr-1 in preventing uncontrolled epidermal growth.
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