title: RNA interference-directed silencing of VPAC1 receptor inhibits VIP effects on both EGFR and HER2 transactivation and VEGF secretion in human breast cancer cells.
abstract: We used small-interference RNA (siRNA) to explore the mechanisms of some vasoactive intestinal peptide (VIP) actions on human breast cancer cells. Transfection of estrogen-dependent (T47D) and estrogen-independent (MDA-MB-468) breast cancer cells with VPAC(1)-receptor siRNA completely abolished VIP stimulatory effect on secretion of the main angiogenic factor, vascular endothelial growth factor (VEGF), and transactivation of epidermal growth factor receptor (EGFR or HER1) and HER2, two members of HER family of tyrosine-kinase receptors. The silencing procedure suggested the involvement of EGFR and HER2 transactivation in VIP-stimulated VEGF secretion. It was further supported by blocking tyrosine kinase activity by the selective HER inhibitors AG-1478 (EGFR) and AG-825 (HER2). Results give value to the specific signaling of VIP through VPAC(1) receptor in human breast cancer cells and support the potential use of VPAC(1)-receptor antagonists in combined targeted therapies for breast cancer. Molecular therapies involving RNA interference of VPAC(1)-receptor expression could also be considered.
authors: Department of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares 28871, Spain.
authors: Ana
authors: A
authors: Valdehita
authors: María J
authors: MJ
authors: Carmena
authors: Ana M
authors: AM
authors: Bajo
authors: Juan C
authors: JC
authors: Prieto
mesh_terms: D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D042461:Vascular Endothelial Growth Factor A; D014660:Vasoactive Intestinal Peptide; C467484:VEGFA protein, human; C508053:ERBB2 protein, human