Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells

Ana Valdehita, Ana M. Bajo, Andrew V Schally, Jozsef L. Varga, María J. Carmena, Juan C. Prieto

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume302
Issue number1
DOIs
StatePublished - Apr 10 2009

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Vasoactive Intestinal Peptide Receptors
Vasoactive Intestinal Peptide
Transcriptional Activation
Cells
Breast Neoplasms
Estrogens
Phosphorylation
Receptor Protein-Tyrosine Kinases
Metalloproteases
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Epidermal Growth Factor
Protein-Tyrosine Kinases
Light
Cell Line
Antibodies
2-aminoethylamide N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine
Therapeutics

Keywords

  • Breast cancer
  • Drug treatment
  • EGFR
  • GHRH analogues
  • HER2
  • VIP receptors

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells. / Valdehita, Ana; Bajo, Ana M.; Schally, Andrew V; Varga, Jozsef L.; Carmena, María J.; Prieto, Juan C.

In: Molecular and Cellular Endocrinology, Vol. 302, No. 1, 10.04.2009, p. 41-48.

Research output: Contribution to journalArticle

Valdehita, Ana ; Bajo, Ana M. ; Schally, Andrew V ; Varga, Jozsef L. ; Carmena, María J. ; Prieto, Juan C. / Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells. In: Molecular and Cellular Endocrinology. 2009 ; Vol. 302, No. 1. pp. 41-48.
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