Cancer Notes F06

8/10/2019 Cancer Notes F06

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Characteristics of Cancer Cells

Obituary brings to light the tragedy of one localfamily (at ALE section of Website)

1. Have lost the genetic ability to stop dividing

Cancer is heritable

Cancer cells give rise to cancer

cells

2. Immortal

3. Not subject to contact inhibition

4. Metastasize:Spread into other tissues5. Are Dedifferentiated

less specialized than the cell it came from)


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Mitosis:division ofthe nucleus

Cytokinesis:division ofcytoplasm

Daughtercells

M-phase

Interphase =

G1, S, G2

S-phase

G2-phase G1-phase

Prep.for division:organelles

duplicate

Cell growth +normal cell

activities

Synthesis of DNA

(chromosomes replicate)

Cellsdivide

The Cell Cycle


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Regulation of Cell Division

What evidence in your own life do you havethat cell division is regulatedby your body?

Left ear is about same size as right ear.

A cut your finger heals, but the skin doesn't justkeep growing!

What normally controls cell division?


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Contact Inhibition

Cells do not normally grow or divide when incontact w/ other Cells

E.g. Cultured cells in a petri dish

will divide until they form a layer one cell thickand then stop when make contact w/ other cells.

Called contact inhibition of cell growth.

Cells also migrate in culture.

Stop moving when touch other cells due to contactinhibition of cell movement.


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Contact inhibitiondoes not occur in Cancerous Cells

Cancerous cells continue growing andmoving when they touch other cells.

They pile up and they migrate to other parts ofthe body -- the cancer spreads.

Growth Factors

made of protein

Chemical messages that control the cell cycle

How do we know the cell cycle is under geneticcontrol?

1 N l ll th


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1. Normal cell growth

2. Basal cell carcinoma

Both daughtercells divideActively dividing cells

(basal cells)

Only one daughterCell divides

Onedaughterdifferentiat

es


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Growth control in a normal cell

Signaling cellGrowth factor (sonic hedgehog)

Growth factor binds to receptor

Receptor sets off a signalcascade to nucleus

target cell entersS-phase and divides,

eventually repairingwound

target cell

Nucleus


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1. Cell mightproduceits owngrowthfactor

Several ways to get faulty growth control in a cancer cell

2. Mutant receptor might turnon even without

binding growth factor

3. Signal cascade mightoccur even without triggerfrom receptor

In each case, cancer cellenters S phase anddivides inappropriately,causing a tumor


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Growth Factors:Stimulate Cell Division

Diffuse through the body, sometimes a longway, bathing many different cells

Bind to Membrane Receptors, like a keyfitting into a lock. stimulate a pathway inside cell that leads to cell

division.

Each receptor binds to a different growthfactor.

Different cell types are stimulated bydifferent growth factors.


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Cancer: Its all in the Genes

Proto-oncogenes:

Genes that code for growth factors

Active in actively dividing tissues (e.g. skin) Sometimes mutate into......

Oncogenes:

genes that cause cancer produce too much growth factor

Over stimulate mitosis

Oncogenes are rarely inherited.....Why?


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Tumor Suppressor Genes

Tumor Suppressor Genes Code for Proteins that turn off mitosis

e.g. p53 gene

p53 Gene Codes for a protein that stops the cell cycle

after G1

Half of all cancers involve p53

One mutant Tumor Suppressor Genedoes not cause cancer....Why?


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p53: A Tumor Suppresser Gene

How many p53 genes did you inherit? Why?

How many p53 genes need to mutate before acell becomes cancerous? Why?


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BRCA 1:Breast Cancer Susceptibility Gene

BRCA 1 is a Tumor Suppresser gene

If a women inherits BRCA 1 she has a

80 to 90%chance of developing breast cancer

40 to 50%chance of ovarian cancer.

Why arent the percentages 100%?

Why are the percentages much lower for theaverage woman?


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The Role of theEnvironment in Causing Cancer

Certain Viruses, toxins, or Radiation may leadto a p53 mutation

A 2nd p53 mutation may lead to one of thefollowing cancers

Cancer of the....

Bladder, blood, brain, breast, colon, esophagus,

liver, lung, spleen, thyroid, etc.

h


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Therapeutic Strategies:Attack Actively Dividing Cells

Since cancer is uncontrolled cell division, alltreatments involve the cell cycle.

Phase-specific chemotherapies Prevent cells from entering S-phase

Block the S-phase

Block the M-phase (mitosis)


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Phase-specific Chemotherapies

1. Prevent cells from entering the S-phase

Block Growth factor receptors on cell membranewith antibody (e.g. Herceptin)

2. Block the S phase

Methotrexate and other chemotherapeutic drugsblock DNA synthesis

3. Block or stop mitosis

Taxol: interferes with the movement of thechromosomes along spindle fibers


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Cells Affected by Chemotherapy

May affect all rapidly dividing cells

Which cells divide rapidly?

Hair follicle cells Skin cells

Cells lining digestive tract

Blood stem cells Divide to produce???

So.... what would be the side effects?


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Side Effects of Chemotherapy

Baldness

Unable to heal wounds

Destroy lining of digestive tract nausea and severe bacterial infection

Decrease Blood cell Production

RBCsAnemia WBCsdecreased ability to fight infections and

kill cancer cells

H


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How toLower your Cancer Risks

Eat plenty of fiber

Fiber speeds passage through digestive tract

Do not smoke

Drink alcohol in moderation or not at all

Exercise regularly

Do not become overweight Limit dietary fat

Limit sun exposure or use sunscreen (SPF 30)

Learn to recognize the warning signs of cancer


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Documents

Cancer Notes F06