The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 40

first identified in viruses capable of inducing tumours in animals and of
transforming cells in vitro, and are altered versions of the normal genes
that control cell growth and function at every level of growth regulation
[41-43]. Although there are still a considerable number of researches being
carried out on oncogenic viruses [44-47], a considerable majority (approxi-
mately 80%) of human cancers is not induced by viruses and apparently
arise from other causes, such as radiation and chemical carcinogens [7,40] .
Furthermore, despite the potent tumourigenic capacity of oncogenes in
appropriate animal hosts, no retrovirus has yet been shown to be directly
oncogenic in humans [18].
Retroviruses have RNA genomes and can replicate through a DNA
intermediate in infected cells. The oncogenes carried by these viruses are
strongly homologous in sequence to normal cellular genes ( proto-oncogenes )
that are highly conserved in evolution [3,18]. In other words, the normal-
cell genes from which the retroviral oncogenes originated are called proto-
oncogenes . Proto-oncogenes are found at all levels of the different signal
transduction cascades that control cell growth, proliferation, and differen-
tiation, and have roles in normal embryonic development. They are impor-
tant cell regulatory genes, in many cases encoding proteins that function in
the signal transduction pathways controlling normal cell proliferation (e.g.,
src , ras , and raf ).
Oncogenes are mutated or abnormally expressed forms of the corre-
sponding proto-oncogenes, whose functions are to encourage and promote
the normal growth and division of cells. When proto-oncogenes mutate to
become carcinogenic oncogenes, the result is excessive cell multiplication.
Consequently, oncogenes are usually expressed at much higher levels than
the proto-oncogenes and are sometimes transcribed in inappropriate cell
types. In some cases, such abnormalities of gene expression are sufficient to
convert a normally functioning proto-oncogene into an oncogene that drives
cell transformation. In addition to such alterations in gene expression, onco-
genes frequently encode proteins that differ in structure and function from
those encoded by their normal homologs.
The process of activation of proto-oncogenes to oncogenes can include
retroviral transduction or retroviral integration, point mutations, insertion
mutations, gene amplification, chromosomal translocation and/or protein-
protein interactions. Point mutations may arise from the action of chemicals
or radiation. Mutation of the coding sequence can result in formation of
hyperactive protein in normal amounts. The mechanism of gene amplifica-
tion can result in overproduction of a normal protein product. DNA rear-
rangement (chromosome translocation) can give rise to elevated cellular
concentrations of the normal protein product or to the expression of new
proteins created by in-frame fusion of coding sequences from separate
genes.
The DNA viruses of the adenovirus, herpesvirus, poxvirus, and papova-
virus families also possess oncogenic potential. Some DNA tumour viruses