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ABSTRACT: Antiproliferative effects of 1,25-dihydroxyvitamin D3
on breast cells: a mini review
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, p21^WAF1/CIP1, TGF-beta-2
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.
[12/20/2001; Brazilian Journal of Medical and Biological Research]
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