# CELL INTERACTIONS DURING MALIGNANT TRANSFORMATION

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 1988 · $141,745

## Abstract

It is proposed to investigate the means whereby growth-inhibited
non-transformed fibroblasts are able cause growth inhibition of
neoplastically transformed fibroblasts.  The biological model used is the
10T1/2 cell culture system which closely reflects events occurring in
vivo.  In this system cAMP enhances cell interactions leading to growth
control.  The goal is to better understand the physiological control of
cell division at the cell population level so that growth control process
can be manipulated in normal and neoplastic cells.  The aims of this
proposal are to critically examine the role of gap-junctions in
transferring growth regulatory information between cells, and to amass
evidence for or against the cAMP as the chemical messenger of growth
control signals.  The first phase of the study will be to determine in
neoplastic cells sensitive or resistant to growth inhibition by contacting
normal cells, whether cAMP can be transferred to the neoplastic cell and
whether the extent of this transfer correlates with the extent of growth
inhibition.  To detect transferred cAMP we shall utilize a sensitive
micro-fluorometric assay for the detection of free catalytic units
liberated by the action of cAMP on cAMP dependent protein kinase.  We will
next examine alterations in protein phosphorylation in general and of gap
junctional components in particular by polyacrylamide gel electrophoresis,
in homogeneous cultures of normal 10T1/2 cells in which drug induced cAMP
elevation also enhances growth control.  Correlations between enhanced
growth control, protein phosphorylation and gap junctional permeance,
measured by a dye-injection technique, will be examined, and the effects of
agents blocking communication such as the tumor promoters evaluated.  Using
the information gained in studies of normal cells, the question of whether
similar events occur in growth inhibited neoplastic cells will be
examined.  Using fluorescent activated cell sorting, neoplastic cells will
be separated from normal cells, their position in the cell cycle determined
and the phosphorylation state of marker proteins determined.  A secondary
question to be addressed is whether carcinogen-initiated cells when growth
arrested by normal cells are in a biological and biochemical state
corresponding to the initiated or neoplastic state.  By these studies of
routes and means of informational transfer between cells, it is hoped to
help identify defects that result in noeplasia.  This research should
narrow the search for the function of oncogene products, and suggest ways
to correct these defects.

## Key facts

- **NIH application ID:** 3178772
- **Project number:** 5R01CA039604-05
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **SAM.gov UEI:** NSCKLFSSABF2
- **Principal Investigator:** JOHN S BERTRAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $141,745
- **Award type:** 5
- **Project period:** 1984-09-01 → 1990-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178772

## Citation

> US National Institutes of Health, RePORTER application 3178772, CELL INTERACTIONS DURING MALIGNANT TRANSFORMATION (5R01CA039604-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178772. Licensed CC0.

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