Bio Cancer

Some genes code for proteins that control movement through the cell cycle

Mutations to these genes may result in un =restrained cell proliferation (tumor

Tumor cells continuously divide if nurtured

• Beninn
• Spherical and well encapsulated

Slow growing

Unlikely to Spread

Still can be dangerous

Ends in -oma

• Malignant
• Irregularly shaped and not well encapsulated

Fast growing

Likely to spread (metatasize)

Malignant tumor is Cancer

Cancers classified based o site of origin

- Caricoma: epithelial tissue

- Sarcoma: connective/muscle/nervous tissue

- Leukemia/Lymphoma: blood cells

Heredutary

• Carcinogen: agent thought to cause cancer
• - Mutagen: agent that mutantes DNA
• Radiation: x-rays, radon, gamma rays, nuclear
• Chemical: diet, smoking
• Viruses: HPV, H. Pylori, hepatitis
• All muturgens are caricinogens, but not all carcinogenes are mutagens

• - Nonmutagenic: may cause cancer, but not through direct mutation (alcohol)

Primary mechanism of cell cycle control

• Activated by Cyclins
• Cdks partner with different cyclins at different points in the cell cycle to promote cell division

• Cdk itself is also controlled by phosphorylation
• - P_i at one site activates Cdk, & at another site deactivates

• Cdk- cyclin complex
• - Also called mitosis- promoting factor (MPF)

Mitogens

PDGF one of the first growth factors identified

PDGF receptor is an RTK that initiates a MAP kinase cascade to signal cell division

Growth factors can overide cellular controls that otherwise inhibt cell division

Unrestrained, uncontrolled growth of cells that have the ability to metastasize

Failure of cell cycle control

Two kinds of genes can distrup the cell cycle when they are mutated

• 1. Tumor- supressor genes
• 2. Proto- Oncogenes

Normal genes involved in signal transduction pathway to signal cell division.

• Oncogene: mutated proto- oncogene that can cause cancer
• - Some encode receptors for growth factors
• if receptor is mutated "on", cell no longer needs growth factors
• Some encode signal transduction proteins

Only one copy of a proto-oncogene needed

Genes that stop cell division

Prevent Cdk/cyclin binding

• Oncogenes "step on the gas"
• Only one copy of a proto-oncogene needed

Genes that stop cell division

Prevent Cdk/ cyclin binding

• Oncogenes "step on the gas"
• Only one copy of oncogene needed
• Tumor supressors "apply the breaks"
• Both coppies of tumor suppressor need mutation

E₂F: transcription factor that causes cell cycle genes to be expressed

Rb binds to and inhibits E₂F

• Cdk/ cyclin phosphorylates Rb
• - Phosphoryylated Rb unable to bind to E₂F

P16 binds to and ihibits Cdk

P53 monitors integrity of DNA

• If DNA damaged, p53
• - Initiate expression of P21
• Binds to and inhibits cyclin from complexing with Cdk
• - Intitiates expression of DNA repair genes
• - Signals apoptosis in damage too extensive

Prevents dividion of cells with DNA damage

• Methylation of DNA typically inactivated those genes
• - Many cancer cells have methylated tumor supressor genes

- Causation or symptom?

• Nondijunction in cells
• - Causacion or symptom?

Surifical Resection

Radiation

• Chemotherapy
• - Traditional
• - Targeted

• Lifestyle
• - Smoking
• - Nutrition
• - Vaccines

• Early Dtetection
• - Biochemical tests
• - Mammograms
• - Colonoscopy

• HER₂ is RTK
• - Growth factor binds and starts transduction

Overexpressed in over 20% of breast cancer

• Herception
• - Antibodies bind to HER₂
• - Target cell for destruction by immune cells

Ras is a G protein that signals cell division

• Mutated in 30 of all cancers
• - Cannot readily brak down GTP (stuck "on")

• Farnesyl transferase finishes Ras production
• -FTI
• - Does not work well in humans (dead end)

Src is a signal transduction kinase

Mutated in 5% of all cancers (hyperactive)

small RNAs against src

Rb inhibits E₂F

• Mutated in 40% of all cancers
• - Defective, cannot bind to E₂F

New inhibitor for E₂F

P53 checks for DNA damage

• Mutated in more than 50% of all cancers
• - 70-80% in lung cancer
• - Defective P₅₃ cannot check DNA

• Onyx-15
• -Normal adenovirus uses E₁B to blcoks action of P₅₃
• - Use E₁B deficient adenovirus

• Telomerase adds telomeres to DNA
• - Normally active in development & germ cells
• - Inhibited in organism

Most cancers probably have muated telomerase inhibitor

New telomerase inhibitor

• The growth of new blood vessels
• - Tumor requires increasing blood supply

Tumor cells secrete angiogenesis signals

• Angiogenesis Inhibits
• - Angiostatin, endostatin

• Requires
• - Breaking away from primary tumor

- Movement to, into, and out of blood vessel

- Enzymes to degrade tissues along the way