# REC-DNA ANALYSIS OF HUMAN HEMATOPOIETIC DIFFERENTIATION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1988 · $258,203

## Abstract

We have recently found that sequences of alpha-tubulin and gamma-
actin cDNA clones derived from the human leukemic cell line HL-60
contain evidence of multiple somatic mutations.  These changes,
occurrings in highly conserved regions, suggest a causual
relationship to the neoplastic growth of HL-60 cells.  The alpha-
tubulin changes include drastic alterations of a GTP-binding site
homology.  Out of the very small number of cancer-cell cytoskeletal
proteins examined by ourselves and others, three have shown
multiple mutations.  Taken together, these and other results have
prompted us to propose the existence of a new class of oncogenes
which involves the cytokeletal system.  Cytoskeletal oncogenes
would appear to have roles different from the nuclear-acting (e.g.
myc, fos) or the growth-factor/receptor/protein-kinase (e.g., vis,
erb-B, ras) classes of oncogenes.  To further define the role of
cystokeletal mutations occurring in neoplastic cells we will first
isolate genomic clones of the mutant gamma-actin and alpha-tubulin
genes from HL-60 cells.  We will then directly test the oncogene
potential of these genes in model systems for multistage
tumorigenesis.  Because of the assistance of expert collaborators
we will be able to test the oncogene potential of these mutant
genes in myeloid, lymphoid and epithelial tumorigenesis in addition
to the more conventional fibroblast systems.  These systems will
permit us to detect collaboration between mutant cytoskeletal genes
and others such as ras and myc.  We may detect such collaborations
as increase in anchorage independence, decreases in latent period
or effects on the invasiveness of resulting tumors.  We will also
use new rapid screening procedures to screen a large number of
tumor cell lines or fresh tumors for evidence of cytoskeletal
mutations in other neoplasms.  RNase A detecting candidate mutants.
The new polymerase Chain Reaction technique provides a rapid way
to clone any such candidates in order to precisely determine the
nature of the mutations involved.  These experiments will test the
suggestion that a high percentage of cancer cells may contain
cytoskeletal mutations and investigate the way in which
cytoskeletal mutations may collaborate with other oncogenes in
cancer initiation or progression.

## Key facts

- **NIH application ID:** 3170165
- **Project number:** 2R01CA032186-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** WINSTON SALSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $258,203
- **Award type:** 2
- **Project period:** 1982-05-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170165

## Citation

> US National Institutes of Health, RePORTER application 3170165, REC-DNA ANALYSIS OF HUMAN HEMATOPOIETIC DIFFERENTIATION (2R01CA032186-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170165. Licensed CC0.

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