# EPIDERMAL GROWTH FACTOR AND PANCREATIC CANCER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 1992 · $196,046

## Abstract

The molecular mechanisms that lead to malignant transformation of
pancreatic exocrine cells and their subsequent growth advantage are not
known.  However, it is established that cultured human pancreatic cancer
cells overexpress the epidermal growth factor receptor (EGFR).  In
contrast, the receptors for insulin, insulin-like growth factor 1 (IGF-
1), tumor necrosis factor (TNF), interferon-gamma (IFN), and
acetylcholine are not overexpressed in these cells.  In addition to
having increased EGFR mRNA levels, these cells produce transforming
growth factor-alpha (TFG-alpha) and avidly bind and internalize EGF and
TFG-alpha.  However, in human pancreatic cancer cells.  EGF is recycled
and is not readily processed into low molecular weight moieties while
TGF-alpha is rapidly degraded.  Although both ligands induce EGFR
tyrosine phosphorylation and enhance phosphatidylinositol hydrolysis in
these cells, their actions on these important biological processes
exhibit quantitative and qualitative differences.  Further, TGF-alpha is
more potent that EGF at stimulating their anchorage-independent growth,
and is less efficient than EGF at down regulating EGFR.  These
observations raise the possibility that EGF and TGF-alpha may exert
complementary effects that together may combine to provide pancreatic
cancer cells with a unique growth advantage.  Indeed, we recently found
that EGFR, EGF, and TGF-alpha are overexpressed in human pancreatic
cancer tissues.  Therefore, in the present proposal we will test the
hypothesis that excessive activation of EGFR by EGF and TGF-alpha may be
of fundamental importance for the growth of human pancreatic cancer
cells.  To test our hypothesis, we will elucidate the mechanisms that
allow EGF and TGF-alpha to exhibit biological differences in pancreatic
cancer cells, study the signal transduction pathways that are activated
by EGF and TGF-alpha in these cells by comparison with normal rat and
human pancreatic duct cells, use specific antisense expression
constructs and/or antisense oligodeoxynucleotides to inhibit TGF-alpha
expression in cultured human pancreatic cancer cells, use similar
techniques as well as dominant EGFR mutations to inhibit EGFR expression
and EGFR-mediated mitogenesis in these cells, and assess the regulation
of TGF-alpha gene expression in relation to the pancreatic
microenvironment.  We will also determine the potential role of EGFR
overactivation in a nude mouse model of pancreatic cancer, and determine
whether TGF-alpha coupled to pseudomonas toxin can inhibit  the growth
of pancreatic cancers.  Finally, we will use the knowledge gained from
our studies to develop a non-invasive diagnostic test for pancreatic
cancer.

## Key facts

- **NIH application ID:** 3179744
- **Project number:** 2R01CA040162-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **SAM.gov UEI:** MJC5FCYQTPE6
- **Principal Investigator:** Murray Korc
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $196,046
- **Award type:** 2
- **Project period:** 1989-04-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179744

## Citation

> US National Institutes of Health, RePORTER application 3179744, EPIDERMAL GROWTH FACTOR AND PANCREATIC CANCER (2R01CA040162-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179744. Licensed CC0.

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