# HETEROGENEITY OF HUMAN COLONIC CARCINOMA

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 1993 · $201,519

## Abstract

This is a competing renewal application for a project which was initiated
in 1978.  The objective of the project was to determine the molecular basis
for biological differences among sub classes of colon carcinoma cells.  It
is ultimately intended to use these differences for new therapeutic
approaches.  The overall objectives of the last period of funding were to
identify and characterize autocrine growth factors produced by previously
identified sub-classes of colon carcinoma cell lines and to determine their
responses to growth factors.  Each of these objectives were accomplished.
The colon carcinoma cell line bank was converted to growth in a chemically
defined medium.  This permitted the determination of the effects of
exogenously added growth factors and combinations of growth factors on
various growth assays of sub-classes of cells.  TGF-alpha and gastin were
identified as autocrine stimulatory factors.  The expression of these
autocrine factors at the mRNA and protein levels as a function of the sub-
classes of carcinoma cells was determined.  The response to the autocrine
stimulatory and inhibitory factors (TGF-beta family) as function of sub-
classes of colon carcinoma was determined.  TGF-beta activity was
associated with repression of c-myc oncogene and induction of extracellular
matrix molecules.  Having identified positive and negative autocrine
factors for colon carcinoma cells, the next logical step is the
characterization of how their expression is controlled by the cells and how
it is affected by exogenous agents.  The specific aims of the renewal
proposal are:  1. Characterize the control of TGF-alpha expression through
the analysis of cis and trans elements of the TGF-alpha elements promoter,
2. Determine control of TGF-alpha expression in colon carcinoma by
exogenous agents using promoter-reporter gene constructs, nuclear runoffs,
Northern analysis of mRNA and protein determination, 3. Characterize the
control of gastin expression in colon carcinoma using the approaches for
TGF-alpha above, 4. Characterize the mechanism of TGF-beta inhibitory
action in colon carcinoma.

## Key facts

- **NIH application ID:** 3172110
- **Project number:** 5R01CA034432-08
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **SAM.gov UEI:** M9ACC5DQCNL6
- **Principal Investigator:** MICHAEL G BRATTAIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $201,519
- **Award type:** 5
- **Project period:** 1982-02-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172110

## Citation

> US National Institutes of Health, RePORTER application 3172110, HETEROGENEITY OF HUMAN COLONIC CARCINOMA (5R01CA034432-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172110. Licensed CC0.

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