Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells.
We analyzed the cross-talk between receptors for vasoactive intestinal peptide (VIP) and the human epidermal growth factor family of tyrosine kinase receptors (HER) in oestrogen-dependent (T47D) and oestrogen-independent (MDA-MB-468) human breast cancer cells. VIP treatment slowly increased the expression levels of EGFR but it rapidly augmented phosphorylation of EGFR and HER2 in both cell lines. This pattern of HERs transactivation was blocked by the specific VIP antagonist JV-1-53, supporting the direct involvement of VIP receptors in formation of P-EGFR and P-HER2. VIP-induced transactivation was also abolished by H89 (protein kinase A inhibitor), PP2 (Src inhibitor) or TAPI-1 (inhibitor of matrix metalloproteases), following a differential pattern. These results shed a new light on the specific signalling pathways involved in EGFR/HER2 transactivation by VPAC receptors and suggest the potential usefulness of VIP receptor antagonists together with current antibodies against EGFR/HER2 and/or tyrosine kinase inhibitors for breast cancer therapy.
Valdehita
Ana
A
Molecular Neuroendocrinology Unit, Department of Biochemistry and Molecular Biology, Alcalá University, 28871 Alcalá de Henares, Spain.
Bajo
Ana M
AM
Schally
Andrew V
AV
Varga
Jozsef L
JL
Carmena
María J
MJ
Prieto
Juan C
JC
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D066246:ErbB Receptors