Why do normal cells divide?

(8.1, 8.2)• Replacement

• Repair

• Growth

• Regeneration

• Formation of sperm

and egg

Cell Division (mitosis)

• All new cells arise from previous

cells

• Some cells reproduce once in a

lifetime

– Example: neurons in the brain

• Some reproduce every few days

– Example: skin cells, embryo

Cells contain DNA

• Chromosomes

– strands of DNA

– Genes (~2% of DNA)

– Chromosomes also

contain proteins

Before a cell can replicate, it must

replicate its DNA – why?

“Parent” cell

“Daughter” cells

The cell cycle (8.4)

Tightly regulated!

Many checkpoints

that delay the cell

cycle until cell is

ready

Mitosis is relatively

fast

“questions” the cell asks at each

checkpoint

• Do I really want to reproduce?

• Was the DNA replicated? correctly?

• Are the chromosomes moving into daughter cells

correctly?

• Are there enough growth factors?

• Is the cell large enough to divide?

• Have mistakes in the DNA been repaired?

• Is the whole process moving at the right rate?

Control of the cell cycle (8.4, 12.2)

To GO (the “pedal”)

A. Growth factors

• Stimulate cells to grow

• Example: growth hormone

B. Growth factor receptors

• allow the cell to respond to a growth

factor

• Example: GH receptor

To SLOW! (the “brake”) Checkpoint proteins

A. Tumor suppressors

• prevent cell from continuing in cell cycle and send

cell to apoptosis if necessary

B. DNA repair proteins

• if DNA cannot be repaired, cell should undergo apoptosis

• Example: UV repair

A leukemia cancer cell in apoptosis

What happens if multiple types of control

genes are mutated in a single cell?

• Extra growth factor?

• A growth factor receptor that is always on

or too many copies?

• Failure of a tumor suppressor?

• Failure of DNA to repair?

Cancer genes

Cancer is a genetic disease = genes are

mutated

Genes that encode normal cell cycle control

proteins are called proto-oncogenes

oncogene = mutated proto-oncogene, can

lead to cancer cell

Proto-oncogene (normal)

-------- oncogene (cancer causing)

• mutation

Cancer is a multi-hit

disease

More than one

mutation in a single

cell required

Characteristics of cancer cells

(8.5 and 12.2)?

How are cancer cells different from normal

cells

1. Immortal (unless killed)cancer cells keep dividing

2. Loss of contact inhibition results in tumor formation

Contact inhibition

3. Changes in cell membrane

NORMAL SKIN CELLS ROUNDED CELL MEMBRANES

4. Angiogenesis – tumor gets its own

blood supply

5. Enlarged nuclei, abnormal chromosomes

Enlarged nuclei in color cancer cells

Translocation in CML

(remember the cytogenetics lab?)

6. Undifferentiated cells

don’t resemble normal cells and grow very fast

7. Escape apoptosis

8. May metastasize

Carcinogenesis tumorigenesis

metastasis (12.2)

a. Mutation in a single cell

b. Second mutation occurs

c. Third mutation in one cell + other mutations

Note: tumor formation

d. Tumor cells invade surrounding tissue

e. metastasis= cancer cells enter blood

vessel

Tumor types

• Malignant = cancer cells invade

surrounding tissues and break off

• Benign tumor

– Benign tumors are in a fibrous capsule

Treatments for cancer (8.5)

• Excision = Remove

cancerous tissue by

surgery

Chemotherapy (drugs)

• The use of chemicals to treat

disease

• stop cell growth in fast

growing cells

– What are normally fast growing

cells?

• Many come from plants

Radiation

– Destroys DNA of fast growing cells, shrinks

tumors, has side effects

Cancer vaccines

• Human papilloma virus (HPV) causes

genital warts

• Over time, in SOME women, this leads to

cervical cancer

• 500,000 cases per year, the vaccine can

prevent most of them

• Gardasil is the name of the vaccine

• Hepatitis vaccine protects against liver

cancer

Risk factors for cancer

Genetics•some people inherit predispositions (cells have at least 1 mutation at birth)

•the older you are the more time for multiple mutations to arise

•20 carcinogens in tobacco smoke

•chemicals, sunlight, X-rays

•fat, meat

Age

Smoking

Environment

Diet

Predisposition genes for cancer

• inherit 2 alleles for each gene

• Example: tumor supressor gene

• Both alleles need to be mutated for cancer

to occur

• BUT, if a person inherits one mutated

allele, then the risk of cancer increases

Breast Cancer (pg 191) as an example

of cancer predisposition genes

• Breast cancer 2nd highest cause of cancer

death in US women (~44,000 women and 400 men/ year)

• BRCA1 gene

200,000/1600 diagnosed

BRCA-1 gene encodes a tumor

suppressor protein

• If both inherited alleles are normal, 13 %

chance of breast cancer

• If one mutant allele is inherited, 30 – 80%

chance of early breast cancer