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Relation between p53, TRL4 and HPV in head and neck tumors

Grant number: 19/19635-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Mirian Galliote Morale
Grantee:Natália Meneses Araújo
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The development of head and neck cancers is usually associated with alcohol consumption and tobacco use, besides of HPV infection. The HPV, through its virals oncoproteins E6/E7 alters the proteins p53, pRb and others. The p53 protein is also frequently altered in HPV negative tumors given that its function is related to response of cellular stress, and could lead cell to apoptosis or senescence. The toll like receptors of innate immune system also show changes in some tumors; may be associated to antitumor mechanisms, such as activation of cytotoxic immune mechanisms against tumor cells, or mechanisms that favor tumor development by triggering the production of proinflammatory cytokines generating a pro-tumor inflammatory microenvironment. Previous work has shown that there is high TLR4 expression in head and neck cancer cell lines and whose activation by LPS may trigger pro-tumor responses. In this project we intend to evaluate the importance of TLR4 in different cell lines of head and neck cancer, according to the presence of HPV infection and different p53 status. Thus, the expression of TLR4 in head and neck tumor cells will initially be analyzed: HPV positive (UPCI-SCC-154), wild p53 and HPV negative (UPCI-SCC-143) and mutant p53 and HPV negative (UPCI-SCC- 078). Next, we intend to evaluate the effect of cisplatin chemotherapy on these tumor lines concomitantly with LPS induction. The importance of this project lies in the need for studies relating the activation of the innate immune system together with the use of treatments to determine possible changes in responses obtained due to the correlation between TLR, p53 pathways and genotoxicity. (AU)