Tumour Pathology 4 Flashcards
What is the cell cycle defined as?
Time between mitotic divisions
What are the external factors that affect cell cycle control?
Hormones
growth factors
cytokines
stroma
(cells and tissues that support and give structure to organs, glands, or other tissues in body)
When is the cell cycle dependant on external stimuli and when is it autonomous?
Prior to restriction point - external stimuli
After restriction point - autonomous
What are the different steps in the cell cycle
G1 - Gap/Growth phase 1 (synthesis of components for DNA synthesis)
S - DNA synthesis
G2 - Gap/Growth phase 2
M - Mitotic phase
Where do checkpoints in the cell cycle exist?
G1
S
G2-M
What is the function of G1 checkpoint
Restriction point, after cell commits no longer needs growth factors
What is the function of G2-M checkpoint
Stops cell cycle if DNA damage
What is the function of growth factors
Bind to specific receptor
Push cell along G1 to restriction point
Describe retinoblastoma
Proteins
Unphosphorylated form is active form
Tumour suppressor - blocks cell cycle progression
What is the function of phosphorylation of retinoblastoma
Unphosphorylated has E2F bound
Phosphorylation releases E2F
E2F activates DNA regulatory sequences, cell cycle goes ahead
What are the environmental factors that can cause genetic damage?
Chemicals
Radiation
Oncogenic viruses
Describe the multistep process of carcinogenesis
Multiple genes need to be abnormal
Genes may be involved in:
Precancer formation
Invasion locally
avoid cell death
How do chemicals cause carcinogenesis?
Oxidising and alkylating agents damage bases
Carcinogens or their metabolites react with DNA forming DNA adducts
Formation of covalently bound products at particular chromosome sites causes cancer
What are the targets for radiation carcinogenesis?
Purine and pyrimidine bases
Which forms of high energy radiation are carcinogenic?
Ultraviolet radiation
X rays
Gamma radiation
What is the function of P53?
Maintains genomic integrity
When do levels of p53 increase?
When cell is damaged
What is the effect of increased levels of P53?
Cell cycle arrest at G1
Facilitates DNA repair
Apoptosis
What is the effect of a mutated P53 gene?
No G1 arrest or repair of DNA
Genetically damaged cells proliferate and form malignant neoplasms
What is an oncogene
Mutated proto-oncogene
Gene with potential to cause cancer
What is a proto-oncogene
Promotes cell through normal cell cycle
How to oncogenes cause cancer
Mutations
Increase oncogene product
Allow protein product to work independently of control mechanisms
What are tumour suppressor genes
Inhibit cell proliferation and tumour formation
Mutation results in loss of/reduced function
How can tumour suppressor genes cause cancer
Mutations
Stop protein product working (e.g. Rb)
Remove regulators of cell proliferation
