cancer- a deeper look (part 4) ms. gaynor honors genetics
TRANSCRIPT
Cancer- A Deeper Look (Part 4)
Ms. GaynorHonors 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 growth-inhibitingprotein
Cell division under control
Defective,nonfunctioningprotein
Cell division notunder 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 – Options:• stimulates repair enzymes to fix DNA
forces cell into G0 resting stage• keeps cell in G1 arrest causes
apoptosis of damaged cell50% cancers have a mutation in p53 gene
p53 is theCell CycleEnforcer
DNA damage is causedby heat, radiation, or chemicals.
p53 allows cellswith repairedDNA to divide.
Step 1
DNA damage iscaused by heat,radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.
Step 3p53 triggers the destruction of cells damaged beyond repair.
ABNORMAL p53
NORMAL p53
abnormalp53 protein
cancercellStep 3The p53 protein fails to stop
cell division and repair DNA.Cell divides without repair todamaged DNA.
Cell division stops, and p53 triggers enzymes to repair damaged region.
Step 2
DNA repair enzyme
p53protein
p53protein
p53 — master regulator gene
• 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 anout-of-controlcar with manysystems 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
Cellularchanges:
DNAchanges:
1
Increasedcell division
Oncogeneactivated
2
Growth of polyp
Tumor-suppressorgene inactivated
3
Growth of malignanttumor (carcinoma)
Second tumor-suppressor geneinactivated
Figure 11.18A
– Cancer in the United States
• 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
What’s the CONNECTION to me?