Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells

1α,25-Dihydroxyvitamin D3 [1α,25(OH) 2D3], the hormonally active form of vitamin D3, has been shown to be a potent negative growth regulator of breast cancer cells both in vitro and in vivo. 1α,25(OH)2D3 acts through two different mechanisms. In addition to regulating gene transcription via its spec...

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Detalles Bibliográficos
Publicado: 2004
Materias:
1α,25(OH)2D3
Breast cancer cells
MAP kinase
Src
Tyrosine phosphatases
VDR
calcitriol
growth factor
mitogen activated protein kinase
mitogen activated protein kinase 1
mitogen activated protein kinase 3
orthovanadic acid
peptide hormone
protein tyrosine kinase
vitamin D receptor
4 amino 5 (4 methylphenyl) 7 (tert butyl)pyrazolo(3,4 d)pyrimidine
4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
calcitriol receptor
enzyme inhibitor
phosphotyrosine
protein kinase p60
protein tyrosine phosphatase
pyrazole derivative
pyrimidine derivative
article
cell membrane
cell strain MCF 7
drug inhibition
enzyme activity
human
priority journal
signal transduction
transcription regulation
breast tumor
cell nucleus
cell proliferation
drug antagonism
drug effect
enzyme activation
enzymology
metabolism
phosphorylation
protein binding
protein transport
serum
tumor cell line
Breast Neoplasms
Calcitriol
Cell Line, Tumor
Cell Membrane
Cell Nucleus
Cell Proliferation
Enzyme Activation
Enzyme Inhibitors
Humans
Mitogen-Activated Protein Kinases
Phosphorylation
Phosphotyrosine
Protein Binding
Protein Transport
Protein-Tyrosine-Phosphatase
Proto-Oncogene Proteins pp60(c-src)
Pyrazoles
Pyrimidines
Receptors, Calcitriol
Serum
Signal Transduction
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v93_n2_p384_Capiati
http://hdl.handle.net/20.500.12110/paper_07302312_v93_n2_p384_Capiati
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:1α,25-Dihydroxyvitamin D3 [1α,25(OH) 2D3], the hormonally active form of vitamin D3, has been shown to be a potent negative growth regulator of breast cancer cells both in vitro and in vivo. 1α,25(OH)2D3 acts through two different mechanisms. In addition to regulating gene transcription via its specific intracellular receptor (vitamin D receptor, VDR), 1α,25(OH) 2D3 induces rapid, non-transcriptional responses involving activation of transmembrane signal transduction pathways, like growth factors and peptide hormones. The mechanisms that mediate the antiproliferative effects of 1α,25(OH)2D3 in breast cancer cells are not fully understood. Particularly, there is no information about the early non-genomic signal transduction effectors modulated by the hormone. The present study shows that 1α,25(OH)2D3 rapidly inhibits serum induced activation of ERK-1 and ERK-2 MAP kinases. The tyrosine kinase Src is involved in the pathway leading to activation of ERK 1/2 by serum. Furthermore, 1α,25(OH)2D3 increases the tyrosine-phosphorylated state of Src and inhibits its kinase activity, while induces the association of the VDR with Src, either in the presence or absence of serum. In parallel, the hormone rapidly increases the amounts of VDR associated to plasma membranes (PM). Pretreatment with the tyrosine phosphatase inhibitors orthovanadate or bpV (phen) prevented mitogen-activated protein kinase (MAPK) inhibition by 1α,25(OH)2D3. These data altogether suggest that 1α,25(OH)2D3 inhibits the MAPK cascade by inactivating Src tyrosine kinase through a mechanism mediated by the VDR and tyrosine phosphatases. © 2004 Wiley-Liss, Inc.

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