carcinogenesis review Flashcards
what is meant by the term carcinogenesis?
The sequence of events leading to the development of cancer
what features do cancers show due to genetic alterations?
Excessive uncontrolled cell proliferation insensitivity to growth inhibitory signals altered cellular metabolism evasion of apoptosis immortality sustained angiogenesis can invade and metastasise can evade the host immune response
what type of gene is activated leading to uncontrolled growth proliferation?
oncogene activation
what stops growth inhibitory cells working?
Tumour suppressor genes become inactivated
What is a proto-oncogene?
A normal gene that causes cell division and are switched on when cell division is needed
what is an oncogene?
A mutated protooncogene meaning they are expressed inappropriately so always promote cell division
What mutations can cause excess oncogene activity?
Point mutations
Deletions
Amplification
Translocation
what is the main relevant oncogene in colorectal cancer?
K’RAS
The RAS group of oncogenes are relevant In colorectal cancer, what is their role?
they encode a signal transduction protein associated with the cell membrane.
What is the mechanism for a normal RAS protein?
Bound to GDP when in the in-active state, bind to GTP when in their active state.
GDP –> GTP (activation) is due to stimulation of tyrosine kinase receptors by growth factors. This stimulates cell growth and replication
Why does a RAS gene mutation lead to increased cell division?
The mutation means decreased GTPase activity, meaning the GTP bound form of RAS is always active so there is constant pro-growth signals.
what is a tumour suppressor gene?
A gene with products that normally stop a cell growing.
what are the two categories of tumour suppressor genes?
Gatekeepers: arrest the cell cycle
Caretakers: repair DNA damage
What tumour suppressor genes are relevant to colorectal cancer?
APC, TP53,MLH1,MSH2
In a normal colonic epithelial cell what is the mechanism for tumour suppression gene; APC?
APC and beta catenin form a complex with one another, this leads to the destruction of beta catenin leaving beta catenin levels low
when the normal epithelial cells are stimulated by WnT molecules the destruction complex is deactivated and beta catenin isn’t broken down so levels increase
Beta catenin then goes to the nucleus and causes cell proliferation
