1. Cancer- A Deeper Look (Part 4)
Ms. Day
Honors Genetics

2. Genes and Cancer Proto-oncogenes (usually OFF)
Genes that create proteins that normally activates cell division
growth factor genes
become oncogenes (cancer-causing) when mutated
Think- “promotes” cell division so only ON during division
Tumor-suppressor genes (usually ON)
normally inhibits (turns “off”) cell division
if switched “OFF” can cause cancer
example: p53 gene

3. Tumor-Suppressor Genes
Mutations that inactivate tumor suppressor genes
Have similar effects as oncogenes
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal growth- inhibiting protein
Cell division
under control
Defective, nonfunctioning protein
Cell division not under control

4. 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.
Old cells have SHORT telomeres!!!
Cancerous cells do not self destruct and continue to divide rapidly producing millions of new cancerous cells.

5. 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.

6. Some mutagens are carcinogenic.
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.

7. Some Carcinogens Radiation – X Rays, UV light
Chemicals – tar from cigarettes
Virus infection – human papilloma virus (HPV) 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.

8. Cancer & Cell Growth Gene p53 plays a key role in G1 checkpoint
Cancer = failure of cell division control
What control is lost?
lose checkpoint “stops”
Gene p53 plays a key role in G1 checkpoint
p53 protein (made by gene 53) STOPS cell division if it detects damaged DNA
Options:
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 is the Cell Cycle Enforcer

9. p53 — master regulator gene (a tumor suppressor 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
cancer
cell
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.

11. 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!

12. What causes these mutations?
Mutations in cells can be triggered by
UV radiation
chemical exposure
radiation exposure
heat
cigarette smoke
pollution
age
genetics

13. Develops in a stepwise fashion
Colon cancer
Develops in a stepwise fashion
Colon wall 1
Increased cell division
Oncogene activated 2
Growth of polyp
Tumor-suppressor gene inactivated 3
Growth of malignant tumor (carcinoma)
Second tumor- suppressor gene inactivated
Cellular changes:
DNA changes:
Figure 11.18A

14. Cancer in the United States

15. 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