E2F2 transcription factor and expression of proto-oncogenes in human embryonic stem cells

• Grant number: 10/52686-5
• Support type: Regular Research Grants
• Duration: June 01, 2011 - May 31, 2013
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Oswaldo Keith Okamoto
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This research project addresses an important safety issue yet to be solved in the field of cell therapy and of critical relevance to the clinical applications of stem cells: the generation of tumors. Although tumors may arise from any type of stem cell, this project will adopt a pre-established human embryonic stem cell (hESC) line as a study model, given the striking association between pluripotency and tumorigenesis. Recent studies from our group have identified genes with aberrant expression in cancer stem cells. Two of these genes, E2F2 and MELK, are involved in cell cycle control and embryonic development. Studies conducted by independent groups indicate that E2F2 positively regulates the expression of MELK and other genes with important function in stem cell self-renewal, embryonic development, and neoplastic transformation, including the genes Bmi-1, c-Myc and b- Myb. Therefore, we will test whether the repression of E2F2 gene is capable of inhibiting self-renewal and tumorigenicity of hESC based on its direct effects on the cell cycle and regulation of proto-oncogene expression. (AU)

Scientific publications

(4)

(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)

GONCALVES DA SILVA, PATRICIA BENITES; TEIXEIRA DOS SANTOS, MARCIA CRISTINA; RODINI, CAROLINA OLIVEIRA; KAID, CAROLINI; LEITE PEREIRA, MARCIA CRISTINA; FURUKAWA, GABRIELA; GIMENES DA CRUZ, DANIEL SANZIO; GOLDFEDER, MAURICIO BARBUGIANI; REILY ROCHA, CLARISSA RIBEIRO; ROSENBERG, CARLA; OKAMOTO, OSWALDO KEITH. High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells. ONCOTARGET, v. 8, n. 12, p. 19192-19204, 2017. Web of Science Citations: 3.

GONCALVES DA SILVA, PATRICIA BENITES; RODINI, CAROLINA OLIVEIRA; KAID, CAROLINI; NAKAHATA, ADRIANA MITI; LEITE PEREIRA, MARCIA CRISTINA; MATUSHITA, HAMILTON; DA COSTA, SILVIA SOUZA; OKAMOTO, OSWALDO KEITH. Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells. Cytotechnology, v. 68, n. 4, p. 1545-1560, AUG 2016. Web of Science Citations: 2.

TEIXEIRA SANTOS, MARCIA CRISTINA; GONCALVES SILVA, PATRICIA BENITES; RODINI, CAROLINA OLIVEIRA; FURUKAWA, GABRIELA; MARCO ANTONIO, DAVID SANTOS; ZANOTTO-FILHO, ALFEU; MOREIRA, JOSE C. F.; OKAMOTO, OSWALDO KEITH. Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma. STEM CELLS AND DEVELOPMENT, v. 24, n. 22, p. 2700-2708, NOV 15 2015. Web of Science Citations: 4.

KAID, CAROLINI; SILVA, PATRICIA B. G.; CORTEZ, BEATRIZ A.; RODINI, CAROLINA O.; SEMEDO-KURIKI, PATRICIA; OKAMOTO, OSWALDO K. miR-367 promotes proliferation and stem-like traits in medulloblastoma cells. Cancer Science, v. 106, n. 9, p. 1188-1195, SEP 2015. Web of Science Citations: 23.