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Vitamin D pathway in canine mammary tumors

Grant number: 10/01837-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2010
Effective date (End): March 31, 2013
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
Principal researcher:Maria Aparecida Azevedo Koike Folgueira
Grantee:Simone Crestoni Fernandes
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Vitamin D may be involved in the control of proliferation, differentiation and apoptosis of breast cells. Evidences suggest that the vitamin D pathway is deregulated in women with breast cancer, as detected by lower 25(OH)D3 or 1,25(OH)2D3 serum concentration as compared with women without breast cancer, of CYP24A1 gene amplification (that codes the enzyme 24 hydroxilase, which reduces tissue concentration of vitamin D active form). Our group results suggest vitamin D concentration that does not induce hypercalcemia may have genomic effects on mammary tumor. On the other hand, there is no knowledge whether serum concentration of vitamin D may influence mammary tumor development in canine species, neither whether the hormone may exert chemoprevention or therapeutic effects, inhibiting the appearance of tumors and malignant cells proliferation. Hence, our aim is to analyze a few aspects of the vitamin D pathway in mammary tumors of the canine species, using tumor tissue culture as a model. Our approach will be to determine 25(OH)D3 serum concentration in bitches with and without mammary tumors. In patients with mammary tumors, vitamin D receptor (VDR, involved in the hormone genomic actions) expression will be evaluated in tumor samples and adjacent mammary gland tissue. Tissue culture from both tumor samples and adjacent mammary gland tissue will be treated with calcitriol 2nM or 0,228nM (concentration that does not induce hypercalcemia and physiological concentration, respectively) or 100nM (pharmacological concentration). Proliferation and apoptosis effects will be evaluated and expression of vitamin D target genes will be determined.

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