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

Publication ,  Journal Article
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 in: Cancer Res
January 15, 2006

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.

Duke Scholars

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

January 15, 2006

Volume

66

Issue

2

Start / End Page

1025 / 1032

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Ligands
  • Humans
  • Glycoproteins
 

Citation

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Zhang, Y., Banerjee, S., Wang, Z., Xu, H., Zhang, L., Mohammad, R., … Sarkar, F. H. (2006). Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer. Cancer Res, 66(2), 1025–1032. https://doi.org/10.1158/0008-5472.CAN-05-2968
Zhang, Yuxiang, Sanjeev Banerjee, Zhiwei Wang, Hu Xu, Liyue Zhang, Ramzi Mohammad, Amro Aboukameel, et al. “Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer.Cancer Res 66, no. 2 (January 15, 2006): 1025–32. https://doi.org/10.1158/0008-5472.CAN-05-2968.
Zhang, Yuxiang, et al. “Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer.Cancer Res, vol. 66, no. 2, Jan. 2006, pp. 1025–32. Pubmed, doi:10.1158/0008-5472.CAN-05-2968.
Zhang Y, Banerjee S, Wang Z, Xu H, Zhang L, Mohammad R, Aboukameel A, Adsay NV, Che M, Abbruzzese JL, Majumdar APN, Sarkar FH. Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer. Cancer Res. 2006 Jan 15;66(2):1025–1032.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

January 15, 2006

Volume

66

Issue

2

Start / End Page

1025 / 1032

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Ligands
  • Humans
  • Glycoproteins