Stromal-Derived Factor-1α Induces a Non-Canonical Pathway to Activate the Endocrine-Linked Tac1 Gene in Non-Tumorigenic Breast Cells
Document Type
Article
Publication Date
3-1-2008
Journal / Book Title
Journal of Molecular Endocrinology
Abstract
The chemokine Stromal-derived factor-1α (SDF-1α) interacts with seven transmembrane (TM) G-protein-coupled receptor (GPR), CXCR4. SDF-1α is linked to inflammation, chemoattraction, cancer metastasis, and hematopoiesis. Tachykinin (Tac1) peptides bind seven transmembranel (TM), GPR and are involved in tumor promotion. SDF-1α regulates Tac1 expression in non-tumorigenic breast cells through a bimodal pattern with repression at high levels through nuclear factor-kappa B (NFΚB) activation. This study focuses on the mechanism of activation at low SDF-1α in MCF12A non-tumorigenic breast cells. Reporter gene assays with the 5′ flanking region of Tac1 (exon 1 omitted) and co-transfection with the repressor of cAMP response element (CREB) (ICER), and transfection with the CRE sites mutated, verified critical roles for CRE sites in SDF-1α-mediated Tac1 activation. Western blots and functional assays with specific inhibitors indicated that SDF-1α phosphorylated CREB (P-CREB) via Gα2-PI3K-protein kinase C (PKC)ζ-p38-extracellular signal-regulated kinase (ERK) and no evidence of cAMP-PKA pathway. This observation is different from previous studies that reported CREB-phosphorylated PKA pathway in the activation of Tac1 in bone marrow stromal cells. This suggests cell specificity in Tac1 expression. In conclusion, this study reports on a non-canonical pathway in Tac1 activation by SDF-1α. This finding is significant, since Tac1 is relevant to breast cancer metastasis, to bone marrow where stromal cells have a significant facilitating function.
DOI
10.1677/JME-07-0111
Montclair State University Digital Commons Citation
Corcoran, Kelly E.; Malhotra, Ashwani; Molina, Carlos; and Rameshwar, Pranela, "Stromal-Derived Factor-1α Induces a Non-Canonical Pathway to Activate the Endocrine-Linked Tac1 Gene in Non-Tumorigenic Breast Cells" (2008). Department of Biology Faculty Scholarship and Creative Works. 282.
https://digitalcommons.montclair.edu/biology-facpubs/282
Published Citation
Corcoran, K. E., Malhotra, A., Molina, C. A., & Rameshwar, P. (2008). Stromal-derived factor-1α induces a non-canonical pathway to activate the endocrine-linked Tac1 gene in non-tumorigenic breast cells. Journal of Molecular Endocrinology, 40(3), 113-123.
