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Abstract:

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.

Registro:

Documento: Artículo
Título:Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells
Autor:Capiati, D.A.; Rossi, A.M.; Picotto, G.; Benassati, S.; Boland, R.L.
Filiación:Instituto de Ingeniería Genética y Biología Molecular, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahía Blanca, Argentina
Dept. Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahía Blanca, Argentina
Palabras clave: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; mitogen activated protein kinase; 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
Año:2004
Volumen:93
Número:2
Página de inicio:384
Página de fin:397
DOI: http://dx.doi.org/10.1002/jcb.20165
Título revista:Journal of Cellular Biochemistry
Título revista abreviado:J. Cell. Biochem.
ISSN:07302312
CODEN:JCEBD
CAS:calcitriol, 32222-06-3, 32511-63-0, 66772-14-3; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; mitogen activated protein kinase, 142243-02-5; orthovanadic acid, 14333-18-7; protein tyrosine kinase, 80449-02-1; phosphotyrosine, 21820-51-9; protein tyrosine phosphatase, 79747-53-8, 97162-86-2; 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; Calcitriol, 32222-06-3; Enzyme Inhibitors; Mitogen-Activated Protein Kinases, EC 2.7.1.37; Phosphotyrosine, 21820-51-9; Protein-Tyrosine-Phosphatase, EC 3.1.3.48; Proto-Oncogene Proteins pp60(c-src), EC 2.7.1.112; Pyrazoles; Pyrimidines; Receptors, Calcitriol
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v93_n2_p384_Capiati

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Citas:

---------- APA ----------
Capiati, D.A., Rossi, A.M., Picotto, G., Benassati, S. & Boland, R.L. (2004) . Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells. Journal of Cellular Biochemistry, 93(2), 384-397.
http://dx.doi.org/10.1002/jcb.20165
---------- CHICAGO ----------
Capiati, D.A., Rossi, A.M., Picotto, G., Benassati, S., Boland, R.L. "Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells" . Journal of Cellular Biochemistry 93, no. 2 (2004) : 384-397.
http://dx.doi.org/10.1002/jcb.20165
---------- MLA ----------
Capiati, D.A., Rossi, A.M., Picotto, G., Benassati, S., Boland, R.L. "Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells" . Journal of Cellular Biochemistry, vol. 93, no. 2, 2004, pp. 384-397.
http://dx.doi.org/10.1002/jcb.20165
---------- VANCOUVER ----------
Capiati, D.A., Rossi, A.M., Picotto, G., Benassati, S., Boland, R.L. Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells. J. Cell. Biochem. 2004;93(2):384-397.
http://dx.doi.org/10.1002/jcb.20165