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Progression and metastasis of prostate cancer in epithelium conditional PTEN-/- or pRb-/-p53-/- deficient mice (Cre/loxP): proliferation and oxidative stress markers

Abstract

Prostate cancer (PCa) is the most common malignancy in men and the second leading cause of male cancer-related deaths in the Western world. The Pten, p53 and pRb tumor suppressor genes are the most frequently mutated/deleted in various human cancers, including PCa. Recent studies emphasize the role of oxidative stress in the initiation and progression of PCa. This project aims to evaluate the process of tumor progression and metastasis of PCa in two strains of knockout mice, the first one exhibits prostate-specific deletion of Pten and the other exhibits prostate-specific deletion of p53 and pRb (generated by the Cre-loxP system). Knockouts and controls animals will be sacrificed at different ages (6, 12 and 18 months - It is already being done) and ventral prostate lobes, lateral, and dorsal anterior will be submitted to histopathological analysis and whole gene expression by microarrays followed by qPCR validation, for identification of candidate genes, with special attention to genes associated with oxidative stress. Validated genes will be followed by immunohistochemistry and Western blotting and will be also evaluated in samples from patients with CaP at different stages of the disease. New antioxidant drugs will be tested and tumor progression will be assessed by in vivo bioluminescence (luciferase). These results may reveal new markers for diagnostic, staging and prognosis of PCa and also new drug for its treatment and prevention. The first year of this project will be carried out at the Cancer Research UK Cambridge Institute at University of Cambridge/UK. (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)
JURMEISTER, SARAH; RAMOS-MONTOYA, ANTONIO; SANDI, CHIRANJEEVI; PERTEGA-GOMES, NELMA; WADHWA, KARAN; LAMB, ALASTAIR D.; DUNNING, MARK J.; ATTIG, JAN; CARROLL, JASON S.; FRYER, LEE G. D.; FELISBINO, SERGIO L.; NEAL, DAVID E. Identification of potential therapeutic targets in prostate cancer through a cross-species approach. EMBO MOLECULAR MEDICINE, v. 10, n. 3 MAR 2018. Web of Science Citations: 11.
PERTEGA-GOMES, NELMA; FELISBINO, SERGIO; MASSIE, CHARLIE E.; VIZCAINO, JOSE R.; COELHO, RICARDO; SANDI, CHIRANJEEVI; SIMOES-SOUSA, SUSANA; JURMEISTER, SARAH; RAMOS-MONTOYA, ANTONIO; ASIM, MOHAMMAD; TRAN, MAXINE; OLIVEIRA, ELSA; DA CUNHA, ALEXANDRE LOBO; MAXIMO, VALDEMAR; BALTAZAR, FATIMA; NEAL, DAVID E.; FRYER, LEE G. D. A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy. JOURNAL OF PATHOLOGY, v. 236, n. 4, p. 517-530, AUG 2015. Web of Science Citations: 34.

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