# ROLES OF MICROFILAMENT PROTEINS IN NEOPLASIA/METASTASIS

> **NIH NIH R01** · PALO ALTO MEDICAL FOUNDATION RES INST · 1991 · $174,624

## Abstract

The goal of this program has been to identify, isolate, characterize, and
study the effects of expression of human genes that, in a fundamental way,
govern the manifestation of the tumorigenic phenotype of human cells.  For
this work the use of a comparative human cell system is emphasized
consisting of diploid/normal fibroblasts, and immortalized/nontumorigenic
fibroblasts and immortalized/tumorigenic fibroblasts.  This comparative
approach has demonstrated that there are significant differences between
the normal and transformed fibroblast strains in a limited set of abundant
proteins which have been identified as microfilament structural proteins -
actins, tropomyosins, and plastins.  A mutant beta-actin gene was
discovered, cloned, and characterized which, when expressed in transfected
cells at high levels, led to tumorigenic conversion of
immortalized/nontumorigenic human fibroblast cells.  Significant changes in
tropomyosin expression were also shown to occur accompanying tumorigenic
conversion of human fibroblasts, and the transformation-sensitive Tm3
isoform was cloned and characterized.  Finally, plastin was discovered and
identified as a family of calcium-binding phosphoproteins whose function is
to bundle actin filaments at the edge of the cell.  The genes for this
family of proteins have been partially cloned and characterized, and it has
been established that the L-plastin isoform is specifically expressed in
hematopoietic cells and induced in a divergent variety of human tumor-
derived cells.  The results of this program indicate that disruption of
normal microfilament function may be a unifying and fundamental change for
all cellular forms of human cancer including metastatic cancer.  This leads
to the hypothesis that changes in the dynamic regulation of the
cytoskeletal microfilament system underlie development of the cancerous
phenotype of the human cell.  To extend this work research will be
continued to:  (1) complete the characterization of the human L- and T-
plastin genes and the comparative characterization of their regulatory
domains to determine the mechanism of activation of the L-plastin gene in
human neoplasia; (2) construct a hematopoietic cell-specific expression
vector using the L-plastin promoter; (3) develop the L-plastin promoter as
a reporter gene for human cell neoplastic transformation; (4) map the
chromosomal location of the L- and T-plastin genes; (5) examine the effects
of induction of L-plastin synthesis in normal cells; (6) determine the
mechanism and cell cycle specificity of plastin phosphorylation and its
relevance to neoplasia; (7) examine the separate and synergistic effects of
L-plastin, tropomyosin, and mutant and wildtype actin expression on
tumorigenesis and metastasis; (8) extend the survey of normal human tissues
and tumors for expression of plastin isoforms; (9) develop an L-plastin
antibody test for nascent human tumors; (10) characterize the expression of
plastin isoforms during embryonic de...

## Key facts

- **NIH application ID:** 3172545
- **Project number:** 2R01CA034763-08
- **Recipient organization:** PALO ALTO MEDICAL FOUNDATION RES INST
- **SAM.gov UEI:** NWV8N28MQND5
- **Principal Investigator:** JOHN C LEAVITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $174,624
- **Award type:** 2
- **Project period:** 1988-03-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172545

## Citation

> US National Institutes of Health, RePORTER application 3172545, ROLES OF MICROFILAMENT PROTEINS IN NEOPLASIA/METASTASIS (2R01CA034763-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172545. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*