Bio Sci 104
Human Cancers (continued)
How about human cancers?
We described convergence of study of retroviral oncogenes
and characterization of regulatory processes that control normal cell growth and proliferation.
most human cancers
caused by viruses. A few exceptions though:
epatitis B infection is associated with increased rates of liver cancer.
2. Some human cancers are even associated with
infections lead to ulcers
; the chronic inflammation and irritation
appears to be associated with elevated levels of
B. Virtually all cancers appear to be due to
: not an infection, but a
genetic change in a normal gene (or genes) leading to loss of growth control.
frequently incurred after birth (i.e. somatic mutation)-
limited to cancer
with remainder of cells in body having wild-type sequence. Chemicals (natural and
man-made: e.g. cigarette smoke, oxygen), radiation (cosmic X-rays), physical insults
(asbestos fibers) can lead to alterations in gene sequence.
Most mutations either neutral
(no phenotypic effects) or are so detrimental to cell that it dies; only rarely does
mutation lead to loss of control of proliferation.
2. Notably, however, some families have
inherited genetic pre-disposition to cancer
(breast cancer, colon cancer, retinoblastomas).
Here, a genetic change is passed on in
all cells contain mutation
(although only some cell types may proliferate to
cause the cancer).
These forms of mutations usually elevate the chances of developing
cancer, but typically these cancers do not have a rapid onset.
II. What is going on in typical human cancers?
A. What is the most likely set of candidates for the somatic mutations involved in clinical
Same set of proto-oncogenes previously discussed
1. First proof of this hypothesis demonstrated by use of a powerful approach to identify
these mutated, cancer-causing genes: cell transfection.
a. Take DNA from human cancers, introduce it into normal cells growing in culture.
b. If mutated gene is dominant, would expect some cells in culture to now become
cancer-like (can be selected by proper growth conditions).
c. First success- obtained DNA from
human bladder cancer
, could make normal mouse
cells become cancer-like.
Isolated gene involved, sequenced it
d. The c-Ras from the bladder cancer had a single point mutation, converting Val 61 to
Glycine, and therefore
lowering GTPase activity leading to hyperactive Ras
e. Just like v-Ras, the mutant c-Ras in bladder cancer was activated as a oncogene
because of a genetic change, leading to hyperactivity.
Note, however, that in the case
of bladder cancer, no virus involved.