Transcript LECTURE #10: Cancer- A Deeper Look

Cancer- A Deeper
Look (Part 4)
Ms. Gaynor
Honors Genetics
Genes and Cancer
• Proto-oncogenes
– Genes that create proteins that normally activates
cell division
• growth factor genes
• become oncogenes (cancer-causing) when mutated
• Tumor-suppressor genes
– normally inhibits (turns “off”) cell division
– if switched “OFF” can cause cancer
– example: p53 gene
• Tumor-Suppressor Genes
– Mutations that inactivate tumor
suppressor genes
• Have similar effects as oncogenes
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal growthinhibiting
protein
Cell division
under control
Defective,
nonfunctioning
protein
Cell division not
under control
What causes cancer?
• Cancer starts with a mutation of a normal
gene.
• Mutated genes that cause cancer are called
oncogenes.
• It is thought that several mutations need to
occur to give rise to cancer
• Cells that are old or not functioning properly
normally self destruct (APOPTOSIS) and are
replaced by new cells.
• Cancerous cells do not self destruct
and continue to divide rapidly
producing millions of new cancerous cells.
Cancer cells are “hungry”…
• Angiogenesis
– is the recruitment of blood vessels from the
network of neighbouring vessels.
• Without blood and the nutrients it carries, a tumor
would be unable to continue growing.
• A factor which brings about a
mutation in DNA is called a
mutagen.
• A mutagen is mutagenic.
• Any agent that causes cancer is
called a carcinogen and is
described as carcinogenic.
Some mutagens are
carcinogenic.
Some Carcinogens
• Radiation – X Rays, UV light
• Chemicals – tar from cigarettes
• Virus infection – papilloma virus
can be responsible for cervical cancer.
• Hereditary predisposition –
Some families are more susceptible
to getting certain cancers.
– Remember you can’t inherit
cancer its just that you maybe
more susceptible to getting it.
Cancer & Cell
Growth
• Cancer = failure of cell division control
• What control is lost?
– lose checkpoint “stops”
• Gene p53 plays a key role in G1 checkpoint
• p53 protein STOPS cell division if it detects
damaged DNA
p53 is the
– Options:
Cell Cycle
Enforcer
• stimulates repair enzymes to fix DNA
forces cell into G0 resting stage
• keeps cell in G1 arrest  causes
apoptosis of damaged cell
50% cancers have a mutation in p53 gene
p53 — master regulator gene
NORMAL p53
p53 allows cells
with repaired
DNA to divide.
p53
protein
DNA repair enzyme
p53
protein
Step 1
Step 2
Step 3
DNA damage is caused
by heat, radiation, or
chemicals.
Cell division stops, and
p53 triggers enzymes to
repair damaged region.
p53 triggers the destruction
of cells damaged beyond repair.
ABNORMAL p53
abnormal
p53 protein
Step 1
Step 2
DNA damage is
caused by heat,
radiation, or
chemicals.
The p53 protein fails to stop
cell division and repair DNA.
Cell divides without repair to
damaged DNA.
Step 3
Damaged cells continue to divide.
If other damage accumulates, the
cell can turn cancerous.
cancer
cell
• http://www.hhmi.org/biointeractive/media/p53-lg.mov
Development of Cancer
• Cancer develops when mutations accumulate:
– unlimited growth
• turn on growth promoter genes
– ignore checkpoints
• turn off tumor suppressor genes (p53)
– escape apoptosis
• turn off suicide genes
– immortality = unlimited divisions
• turn on chromosome maintenance genes
– promotes blood vessel growth
• turn on blood vessel growth genes
– overcome anchor & density dependence
• turn off touch-sensor gene
It’s like an
out-of-control
car with many
systems failing!
What causes these
mutations?
• Mutations in cells can be triggered by




UV radiation
chemical exposure
radiation exposure
heat




cigarette smoke
pollution
age
genetics
– Colon cancer
•
Develops in a stepwise fashion
Colon wall
1
2
3
Cellular
changes:
Increased
cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumorsuppressor gene
inactivated
Figure 11.18A
– Cancer in the United States
What’s the
CONNECTION to me?
• Avoiding carcinogens can reduce the risk
of cancer
– Reducing exposure to carcinogens
(which induce cancer-causing
mutations)
• Making other lifestyle choices
can help reduce cancer risk