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Study of gene and protein expression of the transcription factor AP-1 in cell culture of adrenocortical tumors

Grant number: 11/15777-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2014
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Claudimara Ferini Pacicco Lotfi
Grantee:Marlene Aparecida Ferreira Pinto
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In southern Brazil, the incidence of adrenocortical tumors is about 10-12 times higher than in the rest of the world, with prevalence of pediatric type due to the occurrence of a germline mutation in p53. Progress in understanding the biology of adrenocortical tumors is still incomplete, and most of the molecular markers used in the study are cell cycle regulators genes. AP-1 (activator protein 1) is a dimeric transcription factor composed of several families of proteins which have in common essential domains for dimerization and DNA binding. The subfamilies Jun (c-Jun, JunB and JunD) and Fos (c-Fos, FosB, Fra-1 and Fra-2) are the majority of the proteins that comprise AP-1. The combination of the different proteins determines the specificity, binding affinity and the genes that are regulated. The effects of the Jun family in neoplastic transformation are fundamentally context-dependent so that, clinically, Jun B may be either an oncogene as a tumor suppressor, while the relevance of JunD as regulator of growth is still unclear. c-Jun, on the other hand, seems to enhance proliferation and protect cells from apoptosis. Studies from our laboratory strongly associate the proliferation stimulated by mitogenic factors in the induction of adrenal and specific composition of AP-1, emphasizing the role of c-Jun and JunB, respectively, in proliferation and cell cycle arrest of the adrenal cortex. How AP-1 exerts its oncogenic effect or anti-oncogenic regulating genes involved in regulating proliferation, differentiation, apoptosis, angiogenesis and metastasis is important and is potentially a target for antitumor therapy. In this context, we hypothesize that Jun family proteins, c-Jun, JunB and JunD correlate with cell cycle regulatory proteins in tumors of the adrenal cortex and can be used in diagnosis and prognosis of this type of tumor, or even, potentially, may be therapeutic targets. To test this hypothesis we aim to analyze the pattern of gene expression and Jun family protein in cultured adrenocortical tumor cells obtained from fragments of tumors from patients with different clinical, anatomical and pathological features and its relations with other cell cycle regulators. Used to analyze gene expression of the Jun family, and their relationship with other oncogenes and tumor suppressors, the methodology of PCR array. Validation of protein expression will be performed by immunoblotting and immunocytochemistry.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PINTO, Marlene Aparecida Ferreira. Analysis of JUN and FOS gene expression in adult and pediatric adrenocortical tumor cells.. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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