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

Abstract

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.