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

Markus Wagner, Tracy Cao, Martha E. Lopez, Christopher Hope, Kristi Van Nostrand, Michael S. Kobrin, Hung U. Fan, Markus W. Büchler, Murray Korc

Research output: Contribution to journalArticle

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Abstract

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-α), 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-α, was inhibited by specific anti TGF-α 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-α-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.

Original languageEnglish (US)
Pages (from-to)782-787
Number of pages6
JournalInternational Journal of Cancer
Volume68
Issue number6
DOIs
StatePublished - Dec 11 1996
Externally publishedYes

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Pancreatic Neoplasms
Epidermal Growth Factor Receptor
Transforming Growth Factor alpha
Growth
Epidermal Growth Factor
Clone Cells
Complementary DNA
Alkylating Agents
Northern Blotting
Agar
Tyrosine
Plasmids
Phosphorylation
Ligands
Cell Line
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. / Wagner, Markus; Cao, Tracy; Lopez, Martha E.; Hope, Christopher; Van Nostrand, Kristi; Kobrin, Michael S.; Fan, Hung U.; Büchler, Markus W.; Korc, Murray.

In: International Journal of Cancer, Vol. 68, No. 6, 11.12.1996, p. 782-787.

Research output: Contribution to journalArticle

Wagner, Markus ; Cao, Tracy ; Lopez, Martha E. ; Hope, Christopher ; Van Nostrand, Kristi ; Kobrin, Michael S. ; Fan, Hung U. ; Büchler, Markus W. ; Korc, Murray. / Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. In: International Journal of Cancer. 1996 ; Vol. 68, No. 6. pp. 782-787.
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