Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum

Int J Cancer. 1996 Dec 11;68(6):782-7. doi: 10.1002/(SICI)1097-0215(19961211)68:6<782::AID-IJC16>3.0.CO;2-2.


Human pancreatic cancers over-express the epidermal growth factor receptor (EGF-R) and all 5 known ligands of the EGF family, including EGF, transforming growth factor-alpha (TGF-alpha), amphiregulin, betacellulin and heparin-binding EGF-like growth factor (HB-EGF). The aim of the present study was to confirm the presence of EGF-R-dependent autocrine loops in a human pancreatic cancer cell line and to explore the possibility that interrupting EGF-R activation by introducing a truncated receptor abrogates pancreatic cancer cell growth. The anchorage-independent growth of PANC-1 human pancreatic cancer cells, previously shown to express TGF-alpha, was inhibited by specific anti TGF-alpha antibodies. PANC-1 cells were then either transfected with an expression plasmid encoding a kinase-deficient EGF-R cDNA (HER653) or infected with the same EGF-R cDNA using a retroviral vector. Multiple transfected and infected clones co-expressed the truncated EGF-R and endogenous EGF-R as revealed by Northern blot analysis and immunoblots. In these clones, there was a marked attenuation in EGF- and TGF-alpha-mediated EGF-R tyrosine phosphorylation and c-fos induction. There was also a significant decrease in colony formation in soft agar by comparison with control cells and a significant increase in the effect of the growth-inhibitory effect of the alkylating agent cisplatinum in these clones. Our observations indicate that dominant negative inhibition of EGF-R may have therapeutic potential in pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects*
  • Cisplatin / pharmacology*
  • ErbB Receptors / analysis
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / chemistry
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Antisense / genetics
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Tyrosine / metabolism


  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-fos
  • RNA, Antisense
  • Tyrosine
  • ErbB Receptors
  • Cisplatin