Oral cancer has a high incidence and poor prognosis. Therefore, it is important to understand the mechanism by which the oral cancer can be controlled and to develop new treatment modalities. Experimental studies on animal cancer models, including oral cancer models, as well as clinical trials, have shown that Somatostatin (SS) and Luteinizing Hormone Releasing Hormone (LHRH) exert an inhibitory growth influence on cancers by binding to specific receptors on the cancer cells and activating a tyrosine phosphatase. These results suggest that SS and LHRH, and their analogues, might be able to regulate oral cancer growth through reversal of oncogene effects and have therapeutic value in management of this cancer. Our goal is to determine the feasibility of using analogues of SS and LHRH in oral cancer treatment, and methods to improve their effectiveness.
Our specific aims will be: to determine the relationship between tyrosine phosphorylation of specific membrane proteins and cell growth in oral cancer; to study the regulation of LHRH receptors by phosphorylation of tyrosine proteins; to determine if two kinds of SS receptors exist and to characterize them; to test the regulation of LHRH receptors in models of oral cancer in vivo using hormonal treatment; and, to determine the prevalence of the LHRH receptors in oral human squamous cell carcinoma.
These aims will be accomplished by a series of experiments using oral cancer cell lines, a DMBA Hamster Buccal Cheek Pouch Carcinoma model, and samples from patients with oral cancer. Using these sources, the LHRH and Somatostatin hormone receptors will be studied in terms of their signal transduction and regulation. These studies may lead to a better understanding of the mechanism by which hormones reduce growth in oral cancer and to development of more rational treatment protocols and biochemical predictors of treatment outcome.
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