Oncogenes and Tumor Suppressor Genes
Oncogenes and Tumor
We now recognize that cancer is a
result of a series of specific genetic
changes that take place in a particular
clone of cells. These include alterations
in two types of genes: oncogenes and tumor suppressor genes, and there
are numerous specific genes of each
type now known.
Oncogenes (Gr. onkos, bulk, mass;
+ genos, descent) are genes whose
activity has been associated for some
time with the production of cancer.
They are genes that are normally
found in cells, and in their normal form
they are called proto-oncogenes.
One of these codes for a protein
known as Ras. Ras protein is a guanosine
triphosphatase (GTPase) that is
located just beneath the cell membrane.
When a receptor on the cell surface
binds a growth factor, Ras is activated
and initiates a cascade of reactions,
ultimately leading to cell division.
The oncogene form codes for a
protein that initiates the cell-division
cascade even when the growth factor
has not bound to the surface receptor,
that is, the growth factor is absent.
Of the many ways that cellular DNA can
sustain damage, the three most important
are ionizing radiation, ultraviolet radiation,
and chemical mutagens.The high energy of
ionizing radiation (x rays and gamma rays)
causes electrons to be ejected from the
atoms it encounters, resulting in ionized
atoms with unpaired electrons (free radicals).
The free radicals (principally from
water) are highly reactive chemically, and
they react with molecules in the cell,
including DNA. Some damaged DNA is
repaired, but if the repair is inaccurate, a
mutation results. Ultraviolet radiation is of
much lower energy than ionizing radiation
and does not produce free radicals. It is
absorbed by pyrimidines in DNA and
causes formation of a double covalent
bond between the adjacent pyrimidines.
UV repair mechanisms can also be inaccurate.
Chemical mutagens react with the
DNA bases and cause mispairing during
Gene products of tumor suppressor
genes act as a constraint on cell
proliferation. One such product is
called p53 (for “53-kilodalton protein,”
a reference to its molecular weight).
Mutations in the gene coding for p53
are present in about half of the 6.5 million
cases of human cancer diagnosed
each year. Normal p53 has a number
of crucial functions, depending on the
circumstances of the cell. It can trigger
apoptosis, act as a transcription
activator or repressor (turning genes
on or off), control progression from G1
to S phase in the cell cycle, and promote
repair of damaged DNA. Many of
the mutations known in p53 interfere
with its binding to DNA and thus its