Tumour Pathology 4 Flashcards
How does cell division occur?
Normal cell cycle and mitosis
What do checkpoints do?
- monitor and regulate process
- prevent progression at specific points
Examples of checkpoint and their function?
the G1 checkpoint at the G1/S transition
-Once the cell passes the G1 checkpoint and enters S phase, it becomes irreversibly committed to division.
What is the cell cycle?
The ordered sequence of events that occur in a cell in prep for cell division.
four-stage process in which the cell increases in size (G1), copies its DNA (S), prepares to divide/mitosis (G2, ), and divides (mitosis, or M, stage).
What external factors are involved in cell cycle control?
- hormones
- growth factors
- cytokines
What phases of the cell cycle are referred to as Interphase?
G1
S
G2
Describe some cell cycle checkpoints
If cell size is inadequate, it stops at G1 or G2
- if nutrient supply is inadequate it stops at G1
- DNA is not replicated, it stops at S
- Chromosome mis-alignment, M arrest
What are the checkpoint activators?
- Enzymes
- A catalytic sub-unit activated by a regulatory sub-unit cyclin
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 the active enzyme complex in a cell cycle checkpoint?
A CDK/cyclin complex
How do CDK/Cyclin complexes regulate the cell cycle?
Active CDK/cyclin complex phosphorylates target proteins
- > results in activation/inactivation of target proteins
- > substrate regulate events in the next cell cycle phase
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 pRb is phosphorylated it becomes inactive and loses affinity/activates for 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
- Binds to DNA in response to DNA damage
How does p53 maintain the genomes integrity?
Activation of p53 leads to
- cell cycle arrest at G1 to facilitate DNA repair.
- transcriptional up-regulation of the CDK inhibitor p21 and the GADD45 (growth arrest and DNA damaged genes)
What happens if p53 is mutated?
- Theres no G1 arrest or DNA repair
- So genetically damaged cells proliferate & form malignant neoplasmT
What is carcinogenesis?
- failure of cell cycle control
- balance between proliferation and apoptosis is disrupted
