Oncogenesis Flashcards
List and discuss the 5 steps involved in the Pathogenesis of Oncogenesis
- Induction/initiation/primary mutation
- fixation into genome
- avoidance of apoptosis
- avoidance of immune rejection - Promotion
- stimulation of cell expansion of mutated clone
- continue avoidance of apoptosis
- continued avoidance of immune surveillance - Conversion/transformation
- epigenetic and or secondary mutation.
- immortalisation, activation of genome
- loss of cell contact inhibition
- angiogenesis of primary tumour - Progression
- tertiary mutation
- outgrowth of tumour - Metastasis
- breach of vascular endothelium
- lodging and binding to capillary bed
- invasion of secondary site
List the seven classes of proteins that are involved in controlling cell growth.
Classes 1-7 Growth factor Growth factor receptor Signal transduction proteins Transcription factors Pro or anti-apoptotic proteins Cell cycle control proteins DNA repair proteins
Briefly define and discuss Porto-oncogenes
- are normal cells
- some Porto-oncogenes provide signals that lead to cell divisions
- others regulate apoptosis
- mutation of Porto-oncogenes increase risk of neoplasia
- mutated proto-oncogenes are known as oncogenes
Briefly discuss and define oncogenes
- any gene that causes the transformation of a normal cell into a cancerous cell
- special type are the viral genes that can transform a host cell into a cancerous cell
- oncogenes are the result of the mutation and activation of Porto-oncogenes
Briefly define and discuss mutations
Alterations to the structure of functioning a cell or gene.
Discuss and define mutagens
A substance, preparation or other factor that is capable of inducing mutation. Examples: -radiation and chemicals - chromosome rearrangement - oxidative stress - viral infections
Briefly define and discuss carcinogens
A substance capable of causing cancer in living tissue
List and briefly comment on the 4 classes of mutagens
Radiation and chemicals
- usually cause small genetic change.
Chromosome rearrangement
- occur in meiosis, may result in large changes.
Oxidative stress:
- may be generated via normal metabolism, inflammation etc.
-inflammation cells release many oxidants (O2 and H2O2
- oxidants released in chronic inflammation may damage genes
Viral infections:
-viruses can insert genetic material in their host cells.
What are tumour suppressor genes and what do they do?
Tumour suppressor genes are normal genes that:
- slow down cell division
- repair DNA mistakes
- tell cells when to die
Inactivation of TSG results in unregulated cellular growth which may result in neoplasia
Write brief notes on Tp53
- the Tp p53 codes for synthesis for tumour P53
- stops cells from growing and dividing too fast
- if DNA can be repaired, Tp53 activates repair genes
- if DNA repair cannot be repaired, stops it from dividing and undergoes apoptosis
- mutations of tp53 increases risk of breast cancer
Write brief notes on Rb1
- codes for synthesis of tumour suppressor protein PRB
- under certain conditions Prb stops proteins from triggering DNA replication
- acts as a checkpoint
- plays a role in apoptosis and cellular differentiation
How does the immune system deal with mutated or neoplastic cells? For discuss each pro excess
-The immune system conducts constant surveillance for cancer cells
- several strategies are used by the immune system
NK( Natural killer) cells
* a type of lymphocyte that destroy virus infected cell or tumour cells
* no need for prior activation by immune cells or antibodies
* activated by double stranded RNA
Cytotoxic T-cells
- attack damaged or dysfunctional cells
- antigen presentation induces t-cells to become toxic
CD8 receptors:
- it’s a member and glycoprotein found in the surface of a cytotoxic T-cell
- recognises and und to the abnormal antigens on the surface of diseases cell
- once it binds the cytotoxic T-cell induce destruction of abnormal cell
Antibodies:
- bind to abnormal antigens on the surface of pathological cell inducing their destruction via complement
Macrophages:
- kill Timor cells that have been damaged or marked by complement system
List and briefly explain the key characteristics of neoplastic cells
- self sufficient in growth signals
- do not need external stimuli
- insensitivity to growth inhibitor signals
- not responding to normal proliferation inhibitors
- evasion of apoptosis
- resistant to programmed death inactivation of p53
- defects in DNA repair
- failure to repair DNA caused by carcinogens
- limitless replicators potential
- unrestricted proliferation
- sustained angiogenesis
- grow their own blood supply
- ability to invade local tissue and metastasise
Define the following terms
- Oncogenesis
- Carcinogenesis
- Pathogenesis
- The induction or formation of tumour
- The development of cancerous cells from normal ones
- The production and development of a disease
