# TRANSFORMING GROWTH FACTOR-A REGULATION IN KERATINOCYTES

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1992 · $130,638

## Abstract

Transforming growth factor alpha (TGF/alpha) is a polypeptide mitogen of
the epidermal growth factor (EGF) family that stimulates the replication of
normal human keratinocytes.  TGF/alpha is produced and autoinduced in
cultured human keratinocytes and is expressed in normal epidermis.
Epidermal growth control is complex.  Human keratinocyte cell culture is a
more simplified and representative model to examine autoregulation of
proliferation and differentiation.  The principal objective of these
proposed studies is to examine the role of TGF/alpha expression in the
proliferation an differentiation of human keratinocytes.  We propose that
TGF/alpha is a major autocrine/paracrine growth regulator of keratinocytes
in culture, and expression of TGF/alpha protein stimulates normal epidermal
keratinocyte renewal, re-epithelialization and benign and malignant
epidermal hyperproliferation.  The TGF/alpha autocrine/paracrine loop
mediates growth regulation through the cognate receptor for TGF/alpha, the
EGF receptor.  Additional levels of growth control for keratinocytes
include the negative growth regulator, transforming growth factor beta
(TGF/beta) and other growth regulatory gene products such as c-myc.  In
this application, we propose to identify and characterize specific
biological or chemical factors and culture conditions that modulate
TGF/alpha expression and ligand-receptor activation.  We hypothesize that a
variety of biological substances exert their growth modulatory effects
through the TGF/alpha autocrine/paracrine loop.  Northern blot
hybridization, radioreceptor and radioimmunoassays, biosynthetic labeling
assays, and cellular transfection procedures will be employed to examine
the role of these growth factors, receptors and activation pathways in
growth control of human keratinocytes.  Amplification of TGF/alpha
expression and enhancement of keratinocyte replication may be linked events
in epidermal hyperplasia induced by phorbol ester tumor promoters,
wounding, and other disorders of epidermal hyperproliferation.  Epidermis
is an advantageous model system to examine epithelial growth control
because of tissue accessibility, ability to transfer keratinocytes to
culture and the spectrum of pathology that is exhibited by epidermal
hyperplasia, dysplasia and malignancy.  These studies are designed to
elucidate the function and regulation of TGF/alpha in human keratinocytes
and epidermis and will provide insight into the role of TGF/alpha in normal
and pathologic states of epidermis, including wound healing, psoriasis and
cutaneous carcinoma.

## Key facts

- **NIH application ID:** 3159644
- **Project number:** 5R01AR039547-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** MARK PITTELKOW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $130,638
- **Award type:** 5
- **Project period:** 1991-04-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159644

## Citation

> US National Institutes of Health, RePORTER application 3159644, TRANSFORMING GROWTH FACTOR-A REGULATION IN KERATINOCYTES (5R01AR039547-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159644. Licensed CC0.

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