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Study of superoxide dismutase-2 protein in HPV-mediated cell transformation

Grant number: 15/26327-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): September 01, 2016
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Lara Termini
Grantee:Gabriela Ávila de Grazia
Host 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


Oxidative stress reflects a redox imbalance in the cell in favor of oxidant species, which may result in DNA damage, mitochondrial dysfunction, protein misfolding and lipid peroxidation, among others. As a result, oxidative stress is thought to contribute to diverse pathologies such as cancer, neurological disorders, atherosclerosis, diabetes and asthma. Persistent infection with some human papillomavirus (HPV) types is etiologically associated with cervical cancer, one of the leading causes of cancer related female death worldwide. Moreover, HPV infection is associated with a significant percentage of penile, vulvar, anal and head and neck carcinomas. In cells infected with high-oncogenic risk HPV types the oxidative stress generated by the abnormal keratinocytes metabolism and non-efficient chronic inflammatory response may contribute to the cellular transformation process. Furthermore, expression of E6 and E7 oncoproteins interferes with several DNA repair mechanisms, favoring the accumulation of mutations. Moreover, genomic instability promoted by oxidative stress may favor HPV integration in host cell genome, the main cause of viral persistence and of precursor lesions progression to cancer. The protein superoxide dismutase 2 (SOD2) contributes to cellular homeostasis by catalyzing radical super anion dismutation in oxygen and oxygen peroxide preventing the direct inactivation of biomolecules. In previous studies we observed that SOD2 mRNA upregulation is associated with the resistance to tumor necrosis factor (TNF) antiproliferative effect in HPV-immortalized cells. Besides, we showed the existence of a direct correlation between increased SOD2 protein expression and cervical lesions severity. Finally, we identified SOD2 as an independent predictive marker of inguinal lymph node metastases in patients with penile carcinomas. However, the role of this protein in HPV-associated pathologies has not been investigated in depth. The goal of this study is to determine the involvement of SOD2 in HPV-mediated cell transformation and its value as a predictive marker in pathologies caused by this virus. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LORENZI, NOELY P. C.; TERMINI, LARA; FERREIRA-FILHO, EDSON S.; NUNES, RAFAELLA A. L.; SILVA, GABRIELA A. F.; LEPIQUE, ANA P.; LONGATTO-FILHO, ADHEMAR; TACLA, MARICY; BARACAT, EDMUND C.; VILLA, LUISA L.; et al. A positive HPV test with positive p16/Ki-67 double staining in self-sampled vaginal material is an accurate tool to detect women at risk for cervical cancer. CANCER CYTOPATHOLOGY, v. 130, n. 1, . (15/26573-2, 16/16847-0, 08/57889-1, 15/26327-1)

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