# CYTOPLASMIC FACTORS IN CELLULAR GROWTH

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 1989 · $207,190

## Abstract

The long-term goal of this project is to identify factors
responsible for physiological regulation of liver growth and the
mechanisms through which they operate.  Adult rat liver is
essentially non growing, but capable of intense bursts of
proliferation when activated, especially by partial hepatectomy.
Short-term hepatocyte cultures have demonstrated that certain
hormones and growth factors which stimulate or modulate
hepatocyte proliferation in the animal exert similar effects upon
these cells when isolated and maintained in culture.  We
hypothesize that liver growth is regulated by shifts in balance
among a number of synergistically interacting hormonal signals,
which may vary depending upon the metabolic status of cells.
Resolution of the problem depends upon knowledge of the
molecular mechanisms involved.

This proposal focuses upon the mechanisms of action of certain
hormones that stimulate hepatocyte proliferation:  vasopressin,
and related hormones whose signals operate through
phosphatidylinositol (PI) breakdown, and alpha-2-and beta-
adrenergic agents, and glucagon, which operate through cAMP.
We are studying changes in binding of these hormones to their
surface receptors in normal and regenerating hepatocytes in
culture with and without synergistically acting growth factors.
We will also examine modulation of receptor binding by
heterologous ligands.  Transduction of the hormonal signals via
mechanisms involving calcium mobilization and cAMP will be
compared.  Calhibin, a newly discovered cytoplasmic protein
which inhibits receptor binding of vasopressin, angiotensin II and
alpha-2 adrenergic agonists, will receive special emphasis, being
examined in relation to all of the above variants including its
possible role in growth activation by both Ca2+ and cyclic AMP.
In addition, the role of various gangliosides which can selectively
alter the affinity of receptors for their ligands, will be assessed
by analysis of normal and proliferating hepatocytes with and
without addition of different gangliosides to the medium.
Concurrent analysis of DNA synthesis will serve to correlate all
of the results with hepatocyte proliferation.  Implications of this
research relate to restoration of damaged or diseased liver and
in broader context to developmental disorders and neoplasia.

## Key facts

- **NIH application ID:** 3177882
- **Project number:** 5R01CA039099-06
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **SAM.gov UEI:** FBYMGMHW4X95
- **Principal Investigator:** NANCY L BUCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $207,190
- **Award type:** 5
- **Project period:** 1974-12-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177882

## Citation

> US National Institutes of Health, RePORTER application 3177882, CYTOPLASMIC FACTORS IN CELLULAR GROWTH (5R01CA039099-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177882. Licensed CC0.

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