Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways

Endocrinology. 2011 Mar;152(3):931-45. doi: 10.1210/en.2010-0940. Epub 2010 Dec 29.


Epidermal growth factor through the stimulation of epidermal growth factor receptor (EGFR) plays a critical role in the activation of MAPKs and phosphatidylinositol-3-protein kinase/AKT cell survival pathways attributed in many pathological conditions. At the cellular level, such functions involve EGFR overactivation and phosphorylation. In the present study, we describe that human embryonic kidney-293 cells transfected with somatostatin (SST) receptor 5 (SSTR5) exhibit inhibition of EGFR phosphorylation and modulate MAPK and phosphatidylinositol-3-protein kinase/AKT cell survival signaling. Furthermore, suppression of EGFR by using small interference RNA and an antagonist (AG1478) potentiates the SST effect via activation of SSTR5 on signaling molecules. In wild-type human embryonic kidney-293 cells, EGFR/ErbB2 exists as constitutive heterodimers. The presence of SSTR5 leads to the dissociation of the heteromeric complex of EGFR/ErbB2 and display preferential heterodimerization between SSTR5 and EGFR in an agonist-dependent manner. These findings highlight a new undiscovered mechanism and potential role of SSTR5 to attenuate the EGFR-mediated signaling pathways involved in tumorigenesis. Our data indicate that the activation and/or overexpression of SST receptors along with the inhibition of EGFR will serve as an important therapeutic approach in the treatment of ErbB-positive tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line
  • Cell Proliferation
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation / physiology
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Signal Transduction / physiology*


  • Receptors, Somatostatin
  • somatostatin receptor 5
  • Phosphatidylinositol 3-Kinases
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases