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Role of CYP1A2, CYP3A4 and CYP3A5 genes in the establishment of osteosarcoma and the metastatic microenvironment

Grant number: 13/19166-6
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2014
Effective date (End): February 29, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Silvia Regina Caminada de Toledo
Grantee:Alini Trujillo Paolillo
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Etiology of this tumor still unknown and drug resistance remains an important factor that affects many patients. The difference in treatment response is due to genetic variability between individuals, which generates differences in the profile of drug metabolizing enzymes, for example. Cytochrome P-450 (CYP) enzymes participate in phase I of drugs metabolism and are involved in specific activation and detoxification of a large number of compounds. Therefore it has an important role both in the carcinogenesis processes and metabolism of chemotherapeutic agents. It is known that genes in this study, CYP1A2, CYP3A4 and CYP3A5 participate in hormones metabolism, such as testosterone, estrogen and progesterone, which play an important role in bone formation. Thus, the aim of this study is to evaluate the importance of CYP1A2, CYP3A4 and CYP3A5 genes in the establishment of primary and metastatic osteosarcoma. Therefore, for gene expression analysis of patient samples and cell lines, we will use the method of quantitative real time PCR (qRT-PCR). The gene expression profile of the samples will be related with the clinical outcome and survival of patients, whereas the profile obtained for cell lines treated with cisplatin will be related with results obtained in cells assays, such as proliferation, migration, invasion and cell death.

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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)
TRUJILLO-PAOLILLO, ALINI; TESSER-GAMBA, FRANCINE; PETRILLI, ANTONIO SERGIO; DE SEIXAS ALVES, MARIA TERESA; GARCIA FILHO, REYNALDO JESUS; DE OLIVEIRA, RENATO; CAMINADA DE TOLEDO, SILVIA REGINA. CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response. ONCOTARGET, v. 8, n. 24, p. 38530-38540, . (13/19166-6)

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