Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review

Autor(es)

P. Bortman ; M.A.A.K. Folgueira ; M.L.H. Katayama ; I.M.L. Snitcovsky ; M.M. Brentani

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 35, n. 1, p. 01-09, Jan. 2002.

Resumo

The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the active form of vitamin D3, is an important regulator of calcium homeostasis, exerts antiproliferative effects on various cell systems and can induce differentiation in some kinds of hematopoietic cells. These effects are triggered by its receptor, vitamin D receptor (VDR), a phosphoprotein member of the nuclear receptor superfamily, which functions as a transcriptional factor. VDR binds as a heterodimer with retinoid X receptor (R X R) to hexameric repeats, characterized as vitamin D-responsive elements present in the regulatory region of target genes such as osteocalcin, osteopontin, calbindin-D28K, calbindin-D9K, p21WAF1/CIP1, TGF-ß2 and vitamin D 24-hydroxylase. Many factors such as glucocorticoids, estrogens, retinoids, proliferation rate and cell transformation can modulate VDR levels. VDR is expressed in mammary tissue and breast cancer cells, which are potential targets to hormone action. Besides having antiproliferative properties, vitamin D might also reduce the invasiveness of cancer cells and act as an anti-angiogenesis agent. All of these antitumoral features suggest that the properties of vitamin D could be explored for chemopreventive and therapeutic purposes in cancer. However, hypercalcemia is an undesirable side effect associated with pharmacological doses of 1,25-(OH)2D3. Some promising 1,25-(OH)2D3 analogs have been developed, which are less hypercalcemic in spite of being potent antiproliferative agents. They represent a new field of investigation. (AU)

• Processo FAPESP: 99/00900-2 - Mecanismos de regulação da expressão de RNAm de VDR e caracterização do envolvimento das vias de ação genômica e não genômica da Vitamina D em células HC11 parentais ou transformadas com Hras
• Beneficiário: Patricia Bortman Rozenchan
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 98/16066-9 - Mecanismo de ação antiproliferativa da 1,25 (OH)2D3 em células mamárias murinas HC11 parentais e determinação de causas associadas à resistência ao tratamento em células transformadas com Ha-ras
• Beneficiário: Maria Aparecida Azevedo Koike Folgueira
• Linha de fomento: Auxílio à Pesquisa - Regular