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Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer.

Publication ,  Journal Article
Wang, Z; Sengupta, R; Banerjee, S; Li, Y; Zhang, Y; Rahman, KMW; Aboukameel, A; Mohammad, R; Majumdar, APN; Abbruzzese, JL; Sarkar, FH
Published in: Cancer Res
August 1, 2006

The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy. EGFR-related protein (ERRP), a recently identified pan-erbB inhibitor, has been shown to inhibit growth and induce apoptosis of pancreatic cancer cells in vitro and tumor growth in a xenograft model. However, the precise molecular mechanism(s) by which ERRP exerts its antitumor activity remains unclear. The current investigation was undertaken to delineate the tumor growth inhibitory mechanism(s) of ERRP in pancreatic cancer cells. Using multiple molecular assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis, gene transfection, real-time reverse transcription-PCR, Western blotting, invasion, and electrophoretic mobility shift assay for measuring DNA-binding activity of nuclear factor-kappaB (NF-kappaB), we found that ERRP caused marked inhibition of pancreatic cancer cell growth. This was accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF-kappaB and down-regulation of NF-kappaB downstream genes, such as matrix metalloproteinase-9 and vascular endothelial growth factor, resulting in the inhibition of pancreatic cancer cell invasion through the Matrigel. We also found that down-regulation of Notch-1 by small interfering RNA before ERRP treatment resulted in enhanced cell growth inhibition and apoptosis. Our data suggest that the ERRP-mediated inactivation of EGFR, Notch-1, NF-kappaB, and its downstream target genes contributed to the inhibition of cell growth and invasion. We conclude that ERRP could be an effective agent for inhibiting tumor growth and invasion for the treatment of pancreatic cancer.

Duke Scholars

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

August 1, 2006

Volume

66

Issue

15

Start / End Page

7653 / 7660

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Transcription, Genetic
  • Receptor, Notch1
  • RNA, Small Interfering
  • RNA, Messenger
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • NF-kappa B
  • Matrix Metalloproteinase 9
 

Citation

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Wang, Z., Sengupta, R., Banerjee, S., Li, Y., Zhang, Y., Rahman, K. M. W., … Sarkar, F. H. (2006). Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer. Cancer Res, 66(15), 7653–7660. https://doi.org/10.1158/0008-5472.CAN-06-1019
Wang, Zhiwei, Radha Sengupta, Sanjeev Banerjee, Yiwei Li, Yuxiang Zhang, KM Wahidur Rahman, Amro Aboukameel, et al. “Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer.Cancer Res 66, no. 15 (August 1, 2006): 7653–60. https://doi.org/10.1158/0008-5472.CAN-06-1019.
Wang Z, Sengupta R, Banerjee S, Li Y, Zhang Y, Rahman KMW, et al. Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer. Cancer Res. 2006 Aug 1;66(15):7653–60.
Wang, Zhiwei, et al. “Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer.Cancer Res, vol. 66, no. 15, Aug. 2006, pp. 7653–60. Pubmed, doi:10.1158/0008-5472.CAN-06-1019.
Wang Z, Sengupta R, Banerjee S, Li Y, Zhang Y, Rahman KMW, Aboukameel A, Mohammad R, Majumdar APN, Abbruzzese JL, Sarkar FH. Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer. Cancer Res. 2006 Aug 1;66(15):7653–7660.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

August 1, 2006

Volume

66

Issue

15

Start / End Page

7653 / 7660

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Transcription, Genetic
  • Receptor, Notch1
  • RNA, Small Interfering
  • RNA, Messenger
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • NF-kappa B
  • Matrix Metalloproteinase 9