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New signaling pathways modulated by thyroid hormone receptor (TR) in breast cancer

Grant number: 14/22215-1
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): February 28, 2015
Effective date (End): August 27, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Carolina Migliorini Figueira
Grantee:Jéssica Christina Lóis de Oliveira Campos
Supervisor: Paul Webb
Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
Research place: Houston Methodist Research Institute (HMRI), United States  
Associated to the scholarship:11/23659-2 - Interaction between nuclear receptors TR (thyroid hormone receptor), PPAR (Peroxissome Proliferator-Activated Receptor) and other cell proteins, BP.DD


Breast cancer, presents approximately 1,152,161 new cases each year, being the most common cancer among woman, accounting for 411,093 deaths per year. Evidences about Nuclear Receptors (NRs) participation in breast carcinomas starts from Beatson's experiment, in 1896. Later, estrogen (ER) and progesterone (PR) receptor expression were correlated with tumor response to anti-estrogen therapy, as their hormones were known to drive cell proliferation and promote survival of breast cancer cells. However, all ER/PR-negative breast cancer and 40-50% ER/PR-positive patients are insensitive for anti-estrogens therapy, what made researchers change the focus to every other member of nuclear receptor superfamily. The roles of NRs in proliferation, differentiation, and apoptosis support the idea of its important participation in cancer and countless studies show NRs loss or over expression in neoplastic cells. One of these studies focuses on Thyroid Hormone Receptor (TR) expression in cancer. Although evidences of a relationship between THs and breast cancer development are concrete since 1896, with Beatson's experiment, some in vivo and in vitro results differ substantially. Our yeast two-hybrid and immunoprecipitation experiments show important participation of TR in processes like apoptosis, cell cycle, ubiquitination, and DNA repair that leads us towards cancer direction. We propose to perform follow up studies with TRs partners inside essential breast cancer signaling pathways, aiming to understand TRs regulation in gene and protein expression over time and compare with ER, as well as, in different hormonal conditions (presence and absence of estrogen and T3) by using qPCR and Western blot methods, besides Transactivation assays. In parallel we intend to see how thyroid hormones could be related with an increase or decrease of mammary tumors proliferation and if there is a way to modulate that throughout these nuclear receptors. (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)
CAMPOS, JESSICA L. O.; DORATIOTO, TABATA R.; VIDEIRA, NATALIA B.; RIBEIRO FILHO, V, HELDER; BATISTA, FERNANDA A. H.; FATTORI, JULIANA; INDOLFO, NATHALIA DE C.; NAKAHIRA, MARCEL; BAJGELMAN, MARCIO C.; CVORO, ALEKSANDRA; et al. Protein Disulfide Isomerase Modulates the Activation of Thyroid Hormone Receptors. FRONTIERS IN ENDOCRINOLOGY, v. 9, . (16/22246-0, 13/07937-8, 11/23659-2, 13/08743-2, 14/22215-1)

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