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RNA interference-directed silencing of VPAC₁ receptor inhibits VIP effects on both EGFR and HER2 transactivation and VEGF secretion in human breast cancer cells

Author:
Valdehita, Ana, Carmena, María J., Bajo, Ana M., Prieto, Juan C.
Source:
Molecular and cellular endocrinology 2012 v.348 no.1 pp. 241-246
ISSN:
0303-7207
Subject:
RNA interference, antagonists, breast neoplasms, epidermal growth factor receptors, erbB-2 receptor, humans, neoplasm cells, secretion, small interfering RNA, transcriptional activation, transfection, tyrosine, vascular endothelial growth factors, vasoactive intestinal peptide, vasoactive intestinal peptide receptors
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 VPAC₁-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 VPAC₁ receptor in human breast cancer cells and support the potential use of VPAC₁-receptor antagonists in combined targeted therapies for breast cancer. Molecular therapies involving RNA interference of VPAC₁-receptor expression could also be considered.
Agid:
1045959