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

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?