Tumour Pathology 4 Flashcards
What is the cell cycle?
The time between mitotic divisions
4 phases of the cell cycle?
- Mitosis (M)
- Synthesis of DNA synthesis components (G1)
- DNA synthesis (S)
- Prep for mitosis (G2)
What external factors are involved in cell cycle control?
- Hormones
- Growth Factors
- Cytokines
- stroma
What intrinsic factors help control the cell cycle?
Critical checkpoints such as teh restriction point (R) just before G1.
Crossing these checkpoints requires external stimuli to continue.
What phases of teh cell cycle are referred to as interphase?
G1
S
G2
Describe some cell cycle checkpoints:
- IF teh cell size is inadequate it stops at G1 or G2
- If nutrient supply inadequate, stops at G1
- DNA not replicated, stops at S
- Chromosome mis-alignment, M arrest
What makes up the checkpoints?
Enzymes.
Specifically a catalytic sub-unit activated by a regulatory sub-unit
What are the catalytic sub-units in cell cycle checkpoints?
Cyclin-dependent kinases (CDKs)
What are the regulatory sub-units in cell cycle checkpoints called?
Cyclins
What do call teh active enzyme complex in a cell cycle checkpoint?
A CDK/cyclin complex
How do CDK/Cyclin complexes regulate the cell cycle?
CDK/cyclin complex phosphorylates a substrate
- > substrate is either activated or inactivated
- > substrate regulates the next cell cycle
What two things regulates CDK activity?
- Cyclin production/destruction
- CDK inhibitors (CKIs)
What does the retinoblastoma gene code for?
A protein called pRb
What does pRb do?
When activated it Inactivates E2F transcription factor
applies a brake to the cell cycle
How is E2F normally activated?
By Cyclin D/CDK complex phosphorylating (inactivating) pRb
What are the 3 types of enviromental carcinogens?
Chemicals (e.g. aflatoxin)
Radiation
Oncogenic Viruses (E.g. Herpes, HEp B)
What do you call a section of DNA attached to a chemical carcinogen?
A DNA adduct
What are the purines?
Adenine & guanine
What are the Pyrimidines?
Cytosine & Thymine
Where does radiation damage DNA?
Targets Purine & pyrimidine bases
Name 2 cell cycle regulatory pathways frequently disrupted to cause cancer?
- Cyclin D-pRb-E2F pathway
- p53 pathway
How does a mutated retinoblastoma gene cause cancer?
Mutated REtinoblastoma gene
- > Absetn or inactive pRb
- > Overactive E2F transcription factor
- > drives cell proliferation
Dysregulation at which checkpoint causes most Cancers?
The G1-S checkpoint
What genes are commonly mutated to cause G1-S dysregulation?
Rb (retinoblastoma)
CDK4
Cyclin D
p16
What is teh general purpose of p53?
To maintain genomic integrity
How does p53 maintain the genomes integrity?
p53 builds up in damaged cells:
- cell cycle arrest at G1 to facilitate DNA repair
- in severe cases p53-induced apoptosis
What happens if p53 is mutated?
Theres no G1 arrest or DNA reapir so:
genetically damaged cells proliferate & form malignant neoplasms
