Faculty Collaboration Database

Restoring apoptosis in pancreatic cancer cells by targeting the nuclear factor-kappaB signaling pathway with the anti-epidermal growth factor antibody IMC-C225. J Gastrointest Surg 2003 Jan;7(1):37-43; discussion 43

Date

02/01/2003

Pubmed ID

12559183

DOI

10.1016/s1091-255x(02)00088-4

Scopus ID

2-s2.0-0038717931 (requires institutional sign-in at Scopus site)   65 Citations

Abstract

We have previously demonstrated that RelA is constitutively activated in the majority of human pancreatic cancers and plays an important role in tumorigenesis and metastasis. The antiapoptotic gene bcl-xl is a downstream target of RelA, and regulation of bcl-xl transcription is mediated directly by the nuclear factor kappaB (NF-kappaB) binding sites present in the upstream promoter element of the bcl-xl gene. In this study we investigated the effects of inhibition of epidermal growth factor receptor (EGFR) signaling pathway with the anti-EGFR monoclonal antibody IMC-C225 on constitutive NF-kappaB activation and regulation of apoptosis-related genes in human pancreatic cancer cells. We found that activation of EGFR can be blocked with the anti-EGFR antibody IMC-C225 in the human pancreatic cancer cell line MDA Panc-28, leading to a marked decrease in constitutive NF-kappaB DNA binding activity. Our data also suggest that downregulation of NF-kappaB DNA binding activity by IMC-C225 leads to a decrease in bcl-xl and bfl-1 expression. Therefore, targeting the NF-kappaB signaling pathway with an anti-EGFR antibody may be one strategy to restore apoptosis in human pancreatic cancer cells, thereby enhancing the effect of chemotherapy and radiation therapy.

Author List

Sclabas GM, Fujioka S, Schmidt C, Fan Z, Evans DB, Chiao PJ

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antimetabolites, Antineoplastic
Apoptosis
Blotting, Western
Cell Division
Cetuximab
DNA
Deoxycytidine
Electrophoretic Mobility Shift Assay
ErbB Receptors
Humans
NF-kappa B
Pancreatic Neoplasms
Protein Binding
Signal Transduction
Tumor Cells, Cultured