9.3 Prelude to Cancer
3. Explain how mutations contribute to errors in cell cycle regulation and cancer.
Cancer cells are dividing out of control. They don’t respond to the normal signals regulating cell division (ignore
checkpoints) and instead divide continuously.
Mutations in genes which regulate the cell cycle could lead to cancer.
Proto-oncogenes: genes which stimulate cells to grow and divide under certain circumstances in normal cells (e.g.
genes which allow cells to pass through the G c1eckpoint).
Mutations in these genes could cause cells to divide all the time. If this
happens, the mutant genes are called oncogenes (from Greek ogkos =
tumour, mass) See Fig. 5.12 (left and below)
Tumour-suppressor genes: genes which inhibit cells from dividing and/or
cause cells to die
e.g., gene which could normally keep cells in G
e.g., gene which causes cells with badly damaged DNA to die, such as p53
Mutations in tumour-suppressor genes could also cause cells to divide all
FYI: p53 is a gene of particular interest for cancer researchers because it is found mutant in half of all human
cancers. There are rare inherited mutations in p53 (Li-Frameni syndrome). Non-genetic problems can occur with
the p53 protein as well.
Other causes of cancer:
Viruses such as HPV (human papilloma virus) can bind to an inactivate p53; Sarcomas (a type of tumour) produced
another protein that binds to and inactivates p53 protein, allowing sarcoma cells to continue dividing while
ignoring cell cycle controls.
Carcinogens: molecules which can promote rapid unregulated cell division or cause DNA damage leading to
mutations: compounds in grilled food such as barbequed steaks, compounds such as acrylamide in deep-fried
food (e.g., potato chips and French fries), compounds in tobacco smoke, formaldehyde (a preservative used in
embalming), vinyl chloride (use to make PVC), asbestos, dioxins etc.
Cancer (unregulated cell division) usually requires mutations in more than one gene.
Mutations that occur to cell-cycle control genes can lead to cancer. Examples of cell-cycle control genes are the
proto-oncogene (HER2) which makes the receptor protein in the cell membrane and the tumour suppressor gene
(BRCA2) which makes the protein in the nucleus that checks for DNA damage. If one or both become mutated,
their proteins will no longer function normally and this can lead to cancer. The DNA damage must have resulted in a mutated gene that allows unanchored cells to divide (Normal cells must