Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer.

Published

Journal Article

The erbB family of receptor tyrosine kinases plays critical roles in human cancers, including pancreatic cancer. Discovering a specific agent, which targets multiple members of the erbB family, would be important in pancreatic cancer therapy. Recently, we isolated a novel negative regulator of epidermal growth factor receptor (EGFR), termed EGFR-related protein (ERRP), whose expression attenuates EGFR activation. In the current study, we examined the effects of recombinant ERRP on the growth and ligand-induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member(s) of its family, specifically HER-2. Additionally, we compared the growth inhibitory effect of ERRP with that of Erbitux or Herceptin. Our results showed that ERRP is most effective in inhibiting proliferation of BxPC-3, HPAC, and PANC-1 pancreatic cancer cells. ERRP also inhibited ligand-induced activation of EGFR, HER-2, and HER-3 (ErbB3). In contrast, Erbitux and Herceptin only partially or modestly inhibited activation of EGFR, HER-2, and HER-3. Most importantly, ERRP was found to inhibit pancreatic tumor growth in a severe combined immunodeficient mouse xenograft model. The antitumor activity of ERRP correlates well with tumor differentiation and down-regulation of nuclear factor-kappaB activity. In summary, our results suggest that ERRP is an effective pan-erbB inhibitor, which could be a potential therapeutic agent for pancreatic cancers expressing different levels and subclasses of erbB family of proteins.

Full Text

Duke Authors

Cited Authors

  • Zhang, Y; Banerjee, S; Wang, Z; Xu, H; Zhang, L; Mohammad, R; Aboukameel, A; Adsay, NV; Che, M; Abbruzzese, JL; Majumdar, APN; Sarkar, FH

Published Date

  • January 15, 2006

Published In

Volume / Issue

  • 66 / 2

Start / End Page

  • 1025 - 1032

PubMed ID

  • 16424038

Pubmed Central ID

  • 16424038

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-05-2968

Language

  • eng

Conference Location

  • United States