Download Why do normal cells divide? (8.1, 8.2)

Why do normal cells divide?
(8.1, 8.2)
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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
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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
Translocation in CML
(remember the cytogenetics lab?)
Enlarged nuclei in color cancer cells
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)
Age •the older you are the more time for multiple
mutations to arise
Smoking
Diet
•20 carcinogens in tobacco smoke
•fat, meat
Environment
•chemicals, sunlight, X-rays
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