# CHEMICAL TRANSFORMATION OFMOUSE EPIDERMAL KERATINOCYTES

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 1988 · $96,985

## Abstract

Studies on chemical transformation in vitro have been based primarily on
fibroblastic cells.  While these results have led to insights into the
processes of neoplastic transformation, the majority of human cancers are
derived from cells of epithelial origin.  Many investigators have attempted
to develop a transformation assay based on epithelial cells.  Although some
systems have proved to be relatively successful for assaying chemical
carcinogens, a reproducible assay based on a well-characterized epithelial
cell line does not yet exist.

Recently, an epidermal keratinocyte cell line of murine origin (Balb/MK)
has been developed which possesses stable genetic properties useful for
transformation studies.  Balb/MK cells have an absolute requirement for
epidermal growth factor (EGF) for their continued proliferation.  They also
will undergo terminal differentiation when exposed to high levels of
extracellular calcium.  Previous studies have shown that infection of these
cells by a variety of mammalian retroviruses leads to an abrogation of the
EGF requirement as well as a block in the calcium-induced terminal
differentiation pathway.  Thus, these cells are potentially useful as a
general model for epithelial cell transformation.

Initial studies have shown that the treatment of Balb/MK cells with the
chemical carcinogen 20'-methylcholanthrene (MCA) leads to the isolation of
EGF-independent cell lines in a dose-dependent manner.  In addition, these
chemically treated cells are also blocked in their ability to respond to
calcium-induced terminal differentiation.  Therefore, it is proposed that
the Balb/MK cell line can be used as the basis for a chemical
transformation assay for epithelial cells.  The validity of the system will
be examined by comparing the effects of known chemical carcinogens in vivo
with their effects on the Balb/MK cells.  The growth properties of the
chemically transformed Balb/MK cells will be characterized by known in
vitro parameters as well as assays for tumorigenic potential.  The effects
of carcinogen treatment on the differentiation phenotype of these cells
will be examined by the use of known markers of epidermal differentiation.
Finally, the interaction between viral and chemical transformation of these
cells will be assessed.

## Key facts

- **NIH application ID:** 3178766
- **Project number:** 5R01CA039602-03
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **SAM.gov UEI:** DVL1CMRMWRN9
- **Principal Investigator:** Bernard E. Weissman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $96,985
- **Award type:** 5
- **Project period:** 1985-12-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178766

## Citation

> US National Institutes of Health, RePORTER application 3178766, CHEMICAL TRANSFORMATION OFMOUSE EPIDERMAL KERATINOCYTES (5R01CA039602-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178766. Licensed CC0.

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