# Oncogenic insults within the pancreatic ductal glands produce pre-malignant lesions and PDAC

> **NIH NIH F31** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $39,618

## Abstract

PROJECT SUMMARY
Pancreatic cancer remains a lethal cancer in part because of our lack of understanding of its
progression and pathogenesis. Dysregulation of normal progenitor cells can result in the initiation of
cancer. An often-overlooked epithelial progenitor niche of the pancreas are the pancreatic ductal
glands (PDGs), which are blind outpouches stemming from the main pancreatic duct. Previous
analyses have shown an enrichment of pluripotent potential and pancreatic cancer pathways within
cells of the PDGs. Cells expressing trefoil factor family 2 (TFF2) give rise to differentiated progeny
that migrate to the ductal epithelium during pancreatitis; in-vivo TFF2 knockout experiments have
shown these cells are crucial for regeneration of the ductal epithelium. The contribution of this
progenitor niche to PDAC initiation and progression remains largely unexplored. Transgenic mice
were developed in which expression of Cre-recombinase can be induced within TFF2 expressing
cells (Tff2CreERT). Mice with Cre-dependent oncogenes and a dual-color fluorescent reporter (KrasLSL-
G12D; P53fl/fl or Smad4fl/fl; Rosa26mT/mG) were crossed with these animals allowing for simultaneous
activation of oncogenes and permanent GFP tagging of TFF2 expressing cells of the PDGs and
subsequent progeny. Preliminary data show that TFF2-expressing PDG cells exhibit increased
stemness following oncogenic activation and give rise to a wide spectrum of lineage traced
premalignant lesions and cancers. Our central hypothesis is that the activity of oncogenic insults in
PDG cells with stem-like properties results in unique lineage specification and transformation,
producing premalignant and malignant lesions similar to those observed in humans.

## Key facts

- **NIH application ID:** 10829350
- **Project number:** 5F31CA271724-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Kyle McAndrews
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,618
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829350

## Citation

> US National Institutes of Health, RePORTER application 10829350, Oncogenic insults within the pancreatic ductal glands produce pre-malignant lesions and PDAC (5F31CA271724-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829350. Licensed CC0.

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