# MECHANISMS OF REGULATION OF CELL PROLIFERATION

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1988 · $110,774

## Abstract

This research will test a specific hypothesis which attempts to explain how
peptide growth factors regulate cell-cycle specific gene expression and how
alterations in these mechanisms occur in chemically transformed cells.
Based largely on recent findings in this laboratory, it is postulated that
genes which are specifically induced by epidermal growth factor (EGF) are
regulated in part by a trans-acting repressor of gene transcription and
that repressor activity can be lost as a result of chemically induced
neoplastic transformation.  This model suggests that both mitogen
stimulation and the loss of repressor activity are required for maximum
phenotypic effect.  Thus, this model has implications for multistage
carcinogenesis.  In order to test predictions which arise from this model,
somatic cell hybrids between a nontransformed and chemically transformed
cell line will be derived by fusing clonal transfectants containing two
different dominant selectable markers.  These two cell lines differ
markedly in their patterns of regulation of at least two specific genes in
respnose to EGF and inhibitors of protein synthesis.  Hybrid cells will
allow a determination of the complementation properties of specific
trans-acting gene regulatory factors present in these two cell types.  In
addition hybrid genes will be constructed in which coding sequences for the
E. coli enzyme chloramphenicol acetyltransferase (CAT) are fused to
fragments of EGF-regulated cellular genes whose transcription can be
stimulated by inhibitors of protein synthesis.  These hybrid constructs
will be introduced into nontransformed and chemically transformed cells in
order to further study trans-acting factors involved in regulation.
Finally, soluble extracts from both nontransformed and chemically
transformed cells will be developed which retain the capacity to accurately
transcribe IGF-regulated genes in vitro.  These will be used in
complementation experiments in order to further define the spectrum of
transacting transcription factors present in both cell types.

## Key facts

- **NIH application ID:** 3171445
- **Project number:** 5R01CA033643-06
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** MICHAEL J. GETZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $110,774
- **Award type:** 5
- **Project period:** 1983-02-01 → 1989-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171445

## Citation

> US National Institutes of Health, RePORTER application 3171445, MECHANISMS OF REGULATION OF CELL PROLIFERATION (5R01CA033643-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171445. Licensed CC0.

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