Pathology Week 7 E Flashcards
(43 cards)
Define Oncogenesis
The process initiating and promoting the development of neoplasm through the action of biological, chemical or physical agents
Define pathogenesis
The production and development of disease
Define carcinogenesis
The development of cancer
Define a carcinogen
A substance capable of causing cancer in living tissue
What are the factors that play a role in the pathogenesis of cancer?
Accumulated genetic abnormalities
Environmental carcinogenic insults
Growth factor activation
What is the pathogenesis sequence of cancer?
1 - Induction: fixation into the genome, avoidance of apoptosis and immune rejection.
2 - Promotion: stimulation of cell expansion of mutated clone, continued avoidance of apoptosis and immune surveillance.
3 - Conversion/ Transformation: epigenetic &/or secondary mutation, immortalisation and activation of telomerase allowing limitless cell division, loss of cell contact inhibition, angiogenesis of primary tumour.
4 - Progression: tertiary mutations, outgrowth of tumour
5 - Metastasis: breach of vascular endothelium, lodging and binding of capillary beds, invasion of secondary sites.
What are the 7 classes of proteins controlling cell growth?
I - Growth factors
II - Growth factor receptors
III - Signal transduction proteins
IV - Transcription factors
V - Pro- or anti-apoptotic proteins
VI - Cell cycle control proteins
VII - DNA repair proteins
What is significant about proteins class I-IV?
Mutations changing the structure of expression of proteins in classes I-IV generally give rise to dominantly active oncogenes. Viral proteins that activate growth factor receptors may also induce cancer.
What is the role of class V proteins?
Mutations changing the structure or function of class V proteins reduces the rate of cellular attrition, allowing the cell to live longer. (Makes it less susceptible to apoptosis)
What is the function of class VI proteins?
They act as tumour suppressors. Mutations in the gene creating these proteins is likely to produce proteins that have an altered or impair ability to perform the function of suppressing tumours, therefore the mutant cells have a higher probability of becoming tumour.
What will mutations in a class VII cause?
Mutations greatly increase the probability that the mutant cells will become tumour cells
What are the 2 main types of genes that play a role in cancer development?
Tumour suppressor genes
Oncogenes
What are proto-oncogenes?
Normal genes, some of which provide signals that lead to cell division while other relate to apoptosis. Mutations in proto-oncogenes increases the risk of neoplasia and mutated proto-oncogenes are called oncogenes.
What are oncogenes?
Any gene that causes the transformation of normal cells into cancerous cells. They result from the mutation and activation of proto-oncogenes. The key feature of oncogene activity is that a single altered copy leads to unregulated growth. Cell growth caused by oncogenes can occur in the absence of normal growth signals such as those provided by growth factors.
What are the risk % associated with the BRCA gene in regards to breast cancer and ovarian cancer?
80-90% lifetime risk of beat cancer
40-50% lifetime risk of ovarian cancer
What is the full name for BRCA1?
Breast cancer 1, early onset gene
What is the normal function BRCA1?
Plays a role in maintaining the stability of a cells genetic information and provides instructions for making the BRCA1 protein. It plays a role in DNA repair and a critical role in embryonic development and interacts with other tumour suppressor proteins to regulate cell division.
What is the full name for BRCA2?
Breast cancer 2, early onset gene
What are the normal functions of the BRCA2 gene?
Plats a role in maintaining the stability of a cells genetic information. The gene codes for the BRCA2 protein which has a role in DNA repair. This protein may also have a role in the regulation if
What are tumour suppressor genes?
Normal genes that:
Slow down cell division
Repair DNA mistakes
Tell cells when to undergo apoptosis
Their normal function is to inhibit cell proliferation
What happens when tumour suppressor genes are not activated?
This results in unregulated cell growth and may result in neoplasia
What is TP53?
It is a tumour suppressor gene that codes for the synthesis of tumour protein p53. TP53 stops cells from growing and dividing too fast or in an uncontrolled way. TP53 is located in the nucleus of cells throughout the body where it binds directly to the DNA. If the DNA is able to be repaired TP53 activates repair genes. If the DNA is beyond repair it is prevented from dividing and it undergoes apoptosis. Therefore TP53 prevents the development of tumours by blocking the division of cells with mutated or damaged DNA
What is TP53 also known as?
The guardian of the genome
What will a mutate in TP53 result in?
These TP53 genes will produce faulty P53 proteins, which will be unable to do their job of recognising, repairing or initiating apoptosis in defective DNA.
