Biomedical Engineering Reference
In-Depth Information
2.2. The Genetic Changes and Cancer Genes
Carcinogenesis is initiated either by genetic changes (see [23, 27, 37, 41,
46, 52, 55, 66]) or by epigenetic change through activation of oncogene
product or silencing eects of suppressor genes (see [2, 3, 7, 14, 17, 30, 32,
40, 43, 49, 64]). The genetic change may either be as small as point gene
mutation, or as large as some chromosomal aberrations such as deletion of
chromosomal segments, chromosome inversion and chromosomes translo-
cation leading to mutation or deletion of some cancer genes, or activation
of some dominant cancer genes, or inactivation of some recessive cancer
genes. The cancer genes which contribute to the creation of cancer phe-
notype are the oncogenes (dominant cancer genes), the suppressor genes
(recessive cancer genes) and the mis-match repair genes (MMR) which are
involved in DNA synthesis and repair and/or chromosomal segregation. (As
the suppressor genes, MMR genes are recessive genes.) The oncogenes, the
suppressor genes and the MMR genes are the major genes for the creation
of the cancer phenotype although some other modifying genes may also con-
tribute to cancer through its interaction with proteins of oncogenes and/or
suppressor genes or its interference with some cancer pathways. To date,
about 200 oncogenes and about 50 suppressor genes have been identied.
Oncogenes are highly preserved dominant genes which regulate develop-
ment and cell division. When these genes are activated or mutated, normal
control of cell growth is unleashed, leading to the cascade of carcinogene-
sis. Specically, some of the oncogenes such as the Ras oncogene induces
G
0
!G
1
by functioning as a signal propagator from signal receptor at the
cell membrane to the transcription factors in the cell nucleus in the signal
transduction process. Some of the oncogenes serve as transcription factors
(e.g., myc, jun and fos, etn) to aect DNA synthesis during the S stage
while some other oncogenes serve as anti-apoptosis (e.g. bcl-2) agents.
Suppressor genes are recessive genes whose inactivation or mutation
lead to uncontrolled growth. Mutation or deletion of MMR genes (suppres-
sor genes) lead to microsatellite repeats and create a mutator phenotype,
predisposing the aected cells to genetic instability and to increase mu-
tation rates of many relevant cancer genes. Many of the suppressor genes
either function to control the gap stages (G
1
and G
2
) or by abrogating the
apoptosis process or function to control the activation of an oncogene such
as myc. For example, the protein of the suppressor gene RB forms a com-
plex with E2F and some poked proteins to block transition from G
1
!S;
when the RB gene protein is phosphorylated or the RB gene inactivated
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