VERTEBRATE MODEL OF DIFFERENTIATION/TUMOR SUPPRESSION

Project: Research project

Project Details

Description

The histopathology of cancer suggests a progressive loss of
differentiation, where mature cells are replaced by
less-differentiated
counterparts with embryonic behaviors such as high rates of growth
and
cell migration. Some of the genes controlling these functions may
act in
a tissue-specific manner and potentially function as tumor
suppressor
genes. It is further hypothesized that new tissue-specific tumor
suppressors may be found by the histopathologic examination of
mutant
embryos of the zebrafish (Danio rerio), for abnormal
differentiation in
specific, mature embryonic tissues.

The experimental features of the zebrafish make it a unique
vertebrate
model to find mutants defective in differentiation of specific
tissues.
First, each female is capable of producing an average of about 100
rapidly developing, 1 x 1 x 3 mm, transparent embryos per week,
making it
possible to readily produce and examine thousands of mutant
candidates ex
vivo, at a relatively low cost. Parthenogenesis can be used to
unmask
recessive mutations within one generation in heterozygous parents.
Lethal mutations can also be studied, since the heterozygous
parents
allow one to generate additional mutants for further study or
genetic
mapping. Recent progress in zebrafish genetics makes positional
cloning
possible. The production of many early embryonic developmental
mutants
by other investigators indicates that the zebrafish is a practical
vertebrate model for generating interesting genetic mutations.

These studies are expected to reveal genes important to
differentiation
of specific tissues in the zebrafish. Since human cancers show
abnormal
differentiation, homologues of some of these genes may be affected
in
human cancer. It is hoped that work on such genes, their products,
and
expression, will lead to prognostic and therapeutic tools for
patient
care.
StatusFinished
Effective start/end date4/5/971/31/01

Funding

  • National Cancer Institute
  • National Cancer Institute

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