The purpose of this project is to elucidate the molecular and immune pathogenesis of squamous cell neoplasms of the upper aerodigestive tract, and to enable the development of approaches for molecular and immune therapy for these disorders. Human and murine squamous cell carcinoma cell line models have been developed and used to identify genes that are differentially expressed with tumor progression using molecular and immune assays. Proinflammatory cytokines, related signal transduction pathway molecules, and immediate early transcription factor genes have been shown to be overexpressed or activated with tumor progression, and are associated with aggressive growth and metastasis. The function of these candidate genes following overexpression or inhibition by transfection of tumors with dominant negative constructs has been the subject of recent investigations to identify potential targets for molecular and immune therapy. During the past year, the role of transcription factors NF-kB and AP-1 in expression of angiogenic factors IL-8 and VEGF has been elucidated. Hepatocyte Growth Factor/ MET receptor, Epidermal Growth Factor Receptor and the IL-1 Receptor have been identified as upstream activators of these signal pathways and cytokines. Identification of the role of NF-kB has led to a clinical study of a proteasome inhibitor which inhibits tumor growth and angiogenesis and sensitizes head and neck cancers to radiation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000016-09
Application #
6690276
Study Section
(HNSB)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lu, Hai; Yan, Carol; Quan, Xin Xin et al. (2014) CK2 phosphorylates and inhibits TAp73 tumor suppressor function to promote expression of cancer stem cell genes and phenotype in head and neck cancer. Neoplasia 16:789-800
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