# GROWTH DIFFERENTIATION CONTROL IN PRIMARY KERATINOCYTES

> **NIH NIH R01** · YALE UNIVERSITY · 1988 · $155,765

## Abstract

Primary mouse keratinocytes provide an ideal model for the study
of multistep carcinogenesis.  A unique feature of this system is
that a direct connection can be established between in vitro and
in vivo studies, by grafting of cultured keratinocytes back onto
the animal.  Our approach will involve introduction of activated
growth-regulatory genes (oncogenes) into primary keratinocytes
with evaluation of their possible effects on cells (a) in culture (in
response to calcium, TPA defined media) and (b) in vivo, by
grafting (ability to form well stratified epidermis, Benign or
displastic papillomas, frankly invasive carcinomas).  Oncogenes
will be introduced into cells by means of a retroviral vector (MD)
that we have specifically developed for high expression of foreign
genes into primary keratinocytes.  Genes that will be introduced
into cells include:

1) ras oncogene.  Use of a replication-defective MD-ras virus will
provide a significant contribution to experiments already
underway, concerning the role of ras activation as well as
surrounding normal cells in benign versus malignant
transformation of primary keratinocytes.

2) Nuclear oncogenes.  Preliminary studies with two viruses
carrying the Ela and p53 oncogenes will be directly continued.
Construction of viruses carrying other nuclear oncogenes (myc
and myb) will be undertaken.

3) Growth-factor related genes.  Viruses with genes for EGF and
EGF-receptor and the neu oncogene will be made and used to test
the possible role of these genes during neoplastic evolution of
epidermal cells.

4) Oncogenes in various combinations.  Oncogene-carrying
retroviruses will be constructed that carry different selectable
markers.  These viruses will be used as an alternative approach to
helper virus in testing cooperative effects of various oncogenes in
keratinocyte transformation.

## Key facts

- **NIH application ID:** 3159162
- **Project number:** 1R01AR039190-01A1
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** GIAN-PAOLO DOTTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $155,765
- **Award type:** 1
- **Project period:** 1988-07-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159162

## Citation

> US National Institutes of Health, RePORTER application 3159162, GROWTH DIFFERENTIATION CONTROL IN PRIMARY KERATINOCYTES (1R01AR039190-01A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159162. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*