# THE ROLE OF C-MYC AND OTHER ONCOGENES IN CARCINOGENESIS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1987 · $131,768

## Abstract

The plan of research in this proposal is aimed:  (1) at elucidating the
significance of somatic mutations affecting the structure of c-myc genes
and quantitative abnormalities of c-myc gene expression commonly found in
tumors; and (2) at studying the role of different oncogenes in malignant
transformation of various types of normal cells in vitro and in
carcinogenesis in vivo.  To address the first question, a co-transformation
assay has been adopted in which the EJ ras oncogene and various cloned
human and chicken myc genes are co-transfected into rat embryo cells, with
the appearance of foci indicating the presence of a co-transformationally
active myc gene.  Using this assay, it is possible to determine whether
truncation of the c-myc genes and nucleotide alterations present in the
genes isolated from tumors are important for myc co-transformational
activity.  Normal c-myc genes, as well as tumor-derived myc alleles that
are inactive in this assay in their native form, will be placed under the
transcriptional control of retroviral long terminal repeats to see whether
enhanced transcription of these genes renders them co-transformationally
active.  By placing the various myc alleles under the control of inducible
promoters, such as the human metallothionein promoter and the long terminal
repeat of mouse mammary tumor virus, it will be possible to correlate the
level of expression of various mutant and normal myc genes with
co-transformational activity.  An approach to the second major aim requires
the development of replication-defective murine retroviral vectors which
can deliver various oncogenes to many different types of murine and rat
cells at high efficiency.  Such vectors, derived from Moloney murine
leukemia virus, will be used to introduce myc, ras, B-lym, and other
oncogenes into normal and established lymphoid, hematopoietic, and
fibroblastic cells.  The impact of the presence of active oncogenes in
these cells will be studied in vitro and after introduction of the cells
into host animals.  Particular attention will be paid to:  (1)\the
development of the transformed phenotype and tumors, both immediately and
after the introduction of additional oncogenes; (2) any alterations in the
activity of host cellular genes with the introduction of different
oncogenes; (3) the tissue specificity of the effects of the various
oncogenes; and (4) the functional and differentiated characteristics of the
cells transformed by the oncogene-bearing retroviruses.  These experiments
will explore and attempt to recreate the multistep path towards the
development of malignancies of various types of tissues in animals.  In the
process, a better definition of the role played by different oncogenes will
be obtained, as well as a better understanding of the "pre-malignant" state
that exists prior to the development of overt malignancy.  (X)

## Key facts

- **NIH application ID:** 3177061
- **Project number:** 5R01CA038783-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** William M Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $131,768
- **Award type:** 5
- **Project period:** 1985-07-01 → 1988-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177061

## Citation

> US National Institutes of Health, RePORTER application 3177061, THE ROLE OF C-MYC AND OTHER ONCOGENES IN CARCINOGENESIS (5R01CA038783-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177061. Licensed CC0.

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