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Inhibition of serum-stimulated mitogen activated protein kinase by 1alpha,25(OH)2-vitamin D3 in MCF-7 breast cancer cells.
J Cell Biochem. 2004 Oct 01; 93(2):384-97.JC

Abstract

1alpha,25-Dihydroxyvitamin D3 [1alpha,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. 1alpha,25(OH)2D3 acts through two different mechanisms. In addition to regulating gene transcription via its specific intracellular receptor (vitamin D receptor, VDR), 1alpha,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 1alpha,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 1alpha,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, 1alpha,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 1alpha,25(OH)2D3. These data altogether suggest that 1alpha,25(OH)2D3 inhibits the MAPK cascade by inactivating Src tyrosine kinase through a mechanism mediated by the VDR and tyrosine phosphatases.

Authors+Show Affiliations

Instituto de Ingeniería Genética y Biología Molecular, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15368364

Citation

Capiati, Daniela A., et al. "Inhibition of Serum-stimulated Mitogen Activated Protein Kinase By 1alpha,25(OH)2-vitamin D3 in MCF-7 Breast Cancer Cells." Journal of Cellular Biochemistry, vol. 93, no. 2, 2004, pp. 384-97.
Capiati DA, Rossi AM, Picotto G, et al. Inhibition of serum-stimulated mitogen activated protein kinase by 1alpha,25(OH)2-vitamin D3 in MCF-7 breast cancer cells. J Cell Biochem. 2004;93(2):384-97.
Capiati, D. A., Rossi, A. M., Picotto, G., Benassati, S., & Boland, R. L. (2004). Inhibition of serum-stimulated mitogen activated protein kinase by 1alpha,25(OH)2-vitamin D3 in MCF-7 breast cancer cells. Journal of Cellular Biochemistry, 93(2), 384-97.
Capiati DA, et al. Inhibition of Serum-stimulated Mitogen Activated Protein Kinase By 1alpha,25(OH)2-vitamin D3 in MCF-7 Breast Cancer Cells. J Cell Biochem. 2004 Oct 1;93(2):384-97. PubMed PMID: 15368364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of serum-stimulated mitogen activated protein kinase by 1alpha,25(OH)2-vitamin D3 in MCF-7 breast cancer cells. AU - Capiati,Daniela A, AU - Rossi,Ana M, AU - Picotto,Gabriela, AU - Benassati,Silvia, AU - Boland,Ricardo L, PY - 2004/9/16/pubmed PY - 2005/1/7/medline PY - 2004/9/16/entrez SP - 384 EP - 97 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 93 IS - 2 N2 - 1alpha,25-Dihydroxyvitamin D3 [1alpha,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. 1alpha,25(OH)2D3 acts through two different mechanisms. In addition to regulating gene transcription via its specific intracellular receptor (vitamin D receptor, VDR), 1alpha,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 1alpha,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 1alpha,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, 1alpha,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 1alpha,25(OH)2D3. These data altogether suggest that 1alpha,25(OH)2D3 inhibits the MAPK cascade by inactivating Src tyrosine kinase through a mechanism mediated by the VDR and tyrosine phosphatases. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/15368364/Inhibition_of_serum_stimulated_mitogen_activated_protein_kinase_by_1alpha25_OH_2_vitamin_D3_in_MCF_7_breast_cancer_cells_ L2 - https://doi.org/10.1002/jcb.20165 DB - PRIME DP - Unbound Medicine ER -