Neoplasia 2 Flashcards
What are some important genes in carcinogenesis?
- Oncogenes (accelerators)
- Tumour suppressor genes (brakes)
- DNA repair genes
- miRNA’s (non-coding, controlling factor over the rest of genes
- many others
What are proto-oncogenes?
Normal genes which regulate cell division
Give some examples of proto-oncogenes?
- Growth factors
- Growth factor receptors
- Signal transducers
- Control of gene expression
What are abnormal variants of proto-oncogenes?
- Oncogenes
- They produce oncoproteins
How many genes need to be mutated for oncogenes to cause malignancy?
1
What does mutated growth factor cause?
Increasing the amount of growth factor encourages cells to divide at a greater rate than they normally would do
What is enhanced transcription?
- Translocation
- Chromosome rearrangement
- During cell division parts of the chromosomes break off and attach themselves to the same chromosome or a different chromosome - when this happens sometimes genes become fused with each other ‘hybrid’ gene - product of their expression is different genes
How many genes need to be mutated for tumour suppressor genes to cause malignancy?
2
What happens if tumour suppressor genes are mutated?
The brakes mechanism is lost so there is nothing stopping cells from growing and proliferating at a faster rate
What do tumour suppressor genes do?
- Act to inhibit cell division and suppress growth
- Act as ‘anti-oncogenes’ and act by a variety of mechanisms
What are inherited cancer syndromes (Inherited factors)?
- Single mutant genes, often tumour suppressor genes
- Retinoblastoma, some colon cancers
What is familia cancer (inherited factor)?
- Family clusters
- genes and patterns of inheritance not clear
- breast, ovary, colon
What is defective DNA repair (inherited factors)?
- Increased sensitivity to carcinogens and general increased cancer risk
- Xeroderma pigmentosum
What is P53’s function and where does it act?
- Acts just before the restriction point (at the restriction point the cell cycle stops)
- 2 main functions in response to DNA damage:
- Stops the cell cycle to allow DNA repair
- Apoptosis (if repair not possible)
What systems are affected by cancer?
- other cell division controls
- DNA repair mechanisms
- Apoptosis inhibited
- Stimulation of blood vessel formation
- Destructive enzymes activated
- Cell motility increased
What are the characteristics of cancer?
- Growth rate - must divide quickly
- Growth potential - must be able to detach from surrounding abnormal cells
- Differentiation
- Invasion/destruction
- Avoid apoptosis
- Angiogenesis (formation of new blood vessels)
- Evasion of host defences
- Cell surface change (tumour antigens)
- many others…
What are the 6 main hallmarks for cancer?
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evading apoptosis
What are the malignant tumour modes of spread?
- Local spread
- Lymphatic spread
- Blood spread
- Transcoelomic spread
- Intraepithelial spread
What is metastasis?
Spread of the malignant cells to distant organs forming secondary tumours
What is metastases?
Patterns of spread of cancer cells
How are carcinomas spread?
- Lymphatic
- Blood
How are sarcomas spread?
- blood (lymphatic spread rare)
What are some examples of predictable patterns of spread?
- Lung to local nodes, liver, bone and brain
- Tongue to neck nodes, later lung and spine
What is involved in the ‘metastatic cascade’?
- All steps brought about by all different factors that help tumour cells in invasion
- Tumour cells interact with cells and molecules in the local environment
- Motility is often enhanced
- Tumour cells may:
- Alter adhesion molecules
- Make poor basement membrane
- Increase protease production or reduce inhibitors
- Alter extracellular matrix
