# CYTOPLASMIC FACTORS IN CELLULAR GROWTH

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 1992 · $207,610

## Abstract

Broadly stated the goal is to find how a particular cell type is
selectively induced to grow in response to a body need.  Rat liver, a well
studied model whose cells are normally in a state of growth arrest (G/o
phase), undergoes a remarkable outburst of proliferation activity in
response to a sudden excessive work load, imposed experimentally by partial
hepatectomy.  The aim is to explore molecular mechanisms through which a
physiological work load may be translated into signals that initiate liver
growth.  The question is relevant to restoration or repair of lost or
damaged liver and other tissues, as well as to future development of an
artificial liver, and also to our understanding of neoplasia.  Moreover,
the hepatocyte culture studies that we propose, if successful, could lead
to reduced animal usage.  We plan to address the problem directly and in a
novel way.

The working hypothesis is that a large metabolic imbalance elicits hormonal
responses which comprise one of the signaling mechanisms employed by the
body to impose its demands on target tissues.  The individual needs of the
tissues themselves are mediated by peptide growth factors which act at
short range, primarily within the tissue.  The combined interaction of the
hormone(s) and growth factors initiate growth.  We will focus on whether,
when and in what way combinations of these effectors alter the expression
of four genes:  two with direct roles in glucose metabolism (gt-1 and gt-
2), one that controls a battery of metabolic and related genes and seems
also to depress growth (c/ebp), and one a recognized growth suppressor
(rb), whose involvement in liver growth has not been studied.  Pilot
studies point to growth associated changes in expression of these genes
(mRNA abundance).  To pinpoint stages of the cell cycle at which these
changes occur (most are early), we will monitor expression of known cell
cycle marker genes (oncogenes and others related to growth).  Conduct of
this research involves extensive use of primary hepatocyte cultures and
parallel studies in several whole animal models.  A major determinant of
hepatocyte performance in culture is the extracellular matrix to which the
cells are attached.  In almost universally used conventional culture
systems, hepatocytes rapidly lose certain transcriptional capabilities and
normal programs of gene expression are drastically altered.  Other matrices
offer partial solutions, and the gene studies can progress while we explore
additional matrices that maintain a closer semblance of the hepatocyte
phenotype.  Nearly all of these experiments are in new, unexplored
territory; we emphasize correlation with in vivo studies for assessment of
physiological relevance.  New approaches centered on molecular mechanisms
offer a new look at hepatocyte growth control.

## Key facts

- **NIH application ID:** 3177884
- **Project number:** 5R01CA039099-09
- **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:** 1992
- **Award amount:** $207,610
- **Award type:** 5
- **Project period:** 1984-12-01 → 1995-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177884

## Citation

> US National Institutes of Health, RePORTER application 3177884, CYTOPLASMIC FACTORS IN CELLULAR GROWTH (5R01CA039099-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177884. Licensed CC0.

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