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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todo:paper_07302312_v93_n2_p384_Capiati2023-10-03T15:37:18Z Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells Capiati, D.A. Rossi, A.M. Picotto, G. Benassati, S. Boland, R.L. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_07302312_v93_n2_p384_Capiati |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Capiati, D.A. Rossi, A.M. Picotto, G. Benassati, S. Boland, R.L. |
| author_facet |
Capiati, D.A. Rossi, A.M. Picotto, G. Benassati, S. Boland, R.L. |
| author_sort |
Capiati, D.A. |
| title |
Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells |
| title_short |
Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells |
| title_full |
Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells |
| title_fullStr |
Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells |
| title_full_unstemmed |
Inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(OH)2-vitamin D3 in MCF-7 breast cancer cells |
| title_sort |
inhibition of serum-stimulated mitogen activated protein kinase by 1α,25(oh)2-vitamin d3 in mcf-7 breast cancer cells |
| url |
http://hdl.handle.net/20.500.12110/paper_07302312_v93_n2_p384_Capiati |
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