# GTP ENHANCEMENT OF CAMP BINDING IN HEPATOMAS

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 1987 · $88,092

## Abstract

The administration of dibutyryl cAMP (dbcAMP) causes some animal tumors to
cease growing, suggesting that cAMP inhibits tumor growth.  It has been
suggested that in those tumors which are not inhibited by dbcAMP, the
resistance is due to a deficiency in intracellular binding of cAMP.
Consistent with this hypothesis, a dbcAMP-resistant variant of the Morris
hepatoma has been found to bind less cAMP than do dbcAMPinhibitable
variants.

We have found that in normal rat liver cytosol and nuclei, GTP, in
physiologic concentration (10-4 M), stimulates specific binding of [3H]
cAMP to an Mr 57,000 cAMP binding protein (BP), which is presumably the
regulatory subunit of protein kinase (PK) II.  The effect of GTP requires a
trypsin-labile cofactor, which can be removed using GTP agarose,a nd can be
recovered from the agarose.  In a preliminary study, we have observed a
decrease in the effect of 10-4 M GTP on cAMP binding in a nuclear extract
from a dbcAMP-resistant hepatoma, as compared to a dbcAMP responsive one.
In the proposed project, we wish to explore the hypothesis that in
hepatomas that are not inhibited by dbcAMP, the resistance is due to a
decrease in the binding of cAMP to the GTP-stimulatable cAMP BP.

Studies will be done to elucidate further the mechanism by which GTP
enhances binding of cAMP in normal rat liver.  We  will attempt to purify
the GTP cofactor by gel chromatography, and characterize it by studying its
ability to bind [3H] guanosine imidodiphosphate ([3H] GIDP); to hydrolyze
GTP; to enhance cAMP binding to purified PK II receptor in the presence of
GTP; and to increase the PK activity of the purified PK II complex.  We
will also study GTP stimulation of cAMP binding in nuclear extracts and
cytosol from rat hepatocytes maintained in primary culture,and from several
rat hepatoma variants maintained in tissue culture.  The effect of dbcAMP
on the proliferation of these hepatomas will also be studied.  If
GTP-stimulatable cAMP binding is lower in the dbcAMP-resistant tumors than
in the responsive one, or if it is lower in the tumors than in the
hepatocytes, we will investigate whether this can be explaind by a decrease
in the amount of the GTP-stimulatable BP or its affinity for cAMP; a
decrease in the intrinsic responsiveness of the BP to GTP and added
cofactor; or a change in the properties of the cofactor in these tumors.

## Key facts

- **NIH application ID:** 3171735
- **Project number:** 5R01CA034003-05
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **SAM.gov UEI:** G6VVMPNK4Y48
- **Principal Investigator:** EDWARD M ROSENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $88,092
- **Award type:** 5
- **Project period:** 1983-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171735

## Citation

> US National Institutes of Health, RePORTER application 3171735, GTP ENHANCEMENT OF CAMP BINDING IN HEPATOMAS (5R01CA034003-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171735. Licensed CC0.

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