The goal of this study is to 1)identify and determine the function of the regulatory and structural genes involved in genetic and immunologic mechanisms of tumor progression of squamous cell carcinoma of the upper aerodigestive tract that affect human communication, and 2) determine whether these molecules and mechanisms may serve as potential targets for prevention, diagnosis, or therapy. To identify and determine the role of genes involved in genetic and immunologic mechanisms of tumor progression, the laboratory has developed a murine model of tumor progression of primary and metastatic squamous cell carcinoma. These cell lines are being analyzed using enzyme immunoassays and differential display of differentially expressed messenger RNA to identify immune signaling molecules and other genes that are potentially involved in tumor progression. Human cell lines and tissues are being studied to confirm the relevance of these findings to the pathogenesis of human squamous cell carcinoma of the upper aerodigestive tract. To determine whether these molecules and other immune signaling molecules may serve to regulate or dysregulate host immune defenses, candidate genes will be transfected into target cells from the murine model which do not express the genes to determine if they are necessary or sufficient for the phenotypic differences observed between the primary and metastatic tumor lines. Retroviral constructs are being tested to determine if they provide adequate gene transduction and expression for use as vectors for these genes.
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