Study the regulation of transcription factors SF-1 and LRH-1 in normal and tumor adrenal cells

• Grant number: 11/07656-3
• Support Opportunities: Regular Research Grants
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Claudimara Ferini Pacicco Lotfi
• Grantee: Claudimara Ferini Pacicco Lotfi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The nuclear receptor LRH-1 and SF-1 are involved in the regulation of steroidogenesis in the gonads and adrenal glands and the proliferation in different cell types. The mechanisms of action of these transcription factors and the role of their regulators Dax-1, SHP, USF and Pod-1 in the proliferative effect of normal and tumor cells are not well established. Therefore, we analyzed the role of SF-1 and LRH-1 on proliferation of normal and adrenal tumor cells. To test the hypothesis that SF-1 and LH-1 is important in the adrenal proliferation we will utilize primary cultures of rat adrenal cells and tumor cell lines NCI-H295 and Y-1, and cell cultures of human adrenal tumors (adenomas and carcinomas) that were obtained in our laboratory from fragments of patient's tumors. These different cell types will be transfected with plasmids containing the sequence of Pod-1 to test the importance of controlling this transcription factor on the expression of SF-1 and LRH-1. Analysis of gene and protein expression of transcription factors and their regulators will be made via quantitative PCR and "immunoblotting" in the lines and cell cultures that will be or not transfected with Pod-1. The biological effect of Pod-1 action in different cell types will be examined through the analysis of proliferation and apoptosis and the expression of some proteins related to cell cycle. Furthermore, we analyze the interaction of Pod-1 on the Sf-1 and Lrh-1 promoter in cell types previously mentioned by using chromatin immunoprecipitation assays (ChIP assay). Better understanding of the molecular and biochemical mechanisms involved in the normal process and progression of disease becomes important considering the low survival rate of patients with adrenal carcinoma and the high incidence of pediatric adrenal tumors in Brazil. (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)

SILVEIRA, ELAINE; CAVALCANTE, ISADORA PONTES; KREMER, JEAN LUCAS; RIBEIRO DE MENDONCA, PEDRO OMORI; PACICCO LOTFI, CLAUDIMARA FERINI. The tyrosine kinase inhibitor nilotinib is more efficient than mitotane in decreasing cell viability in spheroids prepared from adrenocortical carcinoma cells. CANCER CELL INTERNATIONAL, v. 18, MAR 1 2018. (11/07656-3)

FRANCA, MONICA MALHEIROS; FERRAZ-DE-SOUZA, BRUNO; LERARIO, ANTONIO MARCONDES; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; PACICCO LOTFI, CLAUDIMARA FERINI. POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells. BIOMED RESEARCH INTERNATIONAL, 2015. (12/21839-6, 11/07656-3)

FRANCA, MONICA MALHEIROS; FERRAZ-DE-SOUZA, BRUNO; LERARIO, ANTONIO MARCONDES; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; PACICCO LOTFI, CLAUDIMARA FERINI. POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells. BIOMED RESEARCH INTERNATIONAL, v. 2015, p. 9-pg., 2015-01-01. (11/07656-3, 12/21839-6)

PASSAIA, BARBARA DOS SANTOS; DIAS, MATHEUS HENRIQUE; KREMER, JEAN LUCAS; RAUBER ANTONINI, SONIR ROBERTO; DE ALMEIDA, MADSON QUEIROZ; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; PACICCO LOTFI, CLAUDIMARA FERINI. TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors. FRONTIERS IN ENDOCRINOLOGY, v. 9, FEB 22 2018. (11/07656-3)