Tumour Pathology 4 Flashcards
Describe signal transduction in the cell cycle.
Signal transduction molecules attach to a receptor (as a ligand) and change the shape of the inside part of the receptor.
This alteration allows the receptor to recruit a molecule inside the cell.
The messenger molecule can be activated and released and travel to its target in the cytoplasm or the nucleus.
Usually go to the nucleus (post signal transduction)
Describe transcription factors.
Transcription factors bind segments of DNA called promoters (which can inhibit).
They usually activate transcription of the gene by recruitment of the enzyme which transcribes DNA to RNA.
(its importance)
Describe the Restriction Point
“the point og no return” in the cell cycle.
In G1 (gap or growth phase).
Beyond the restriction point, the cell commits to the cell cycle and is no longer dependent on growth factors.
Describe the G2-M checkpoint.
This checkpoint stops the cell cycle is there is DNA damage
By the “KEY PROTEIN”
Describe the regulation of the restriction point.
The retinoblastoma protein acts as a tumour suppressor gene as it blocks the continuation of the cell cycle.
If only a few phosphate groups are present, then the cell will stay in G1.
In this instance, the Rb protein binds a transcription factor called E2F. This transcription factor cannot function if it is bound
If numerous phosphate groups are present then the cell progresses through the cell cycle.
In this instance the phosphate groups change the shape of Rb protein and it releases the E2F molecule (Rb = inactive).
The E2F molecules then bind various DNA regulatory sequences (e.g. promtors) and the cell cycle progresses.
Describe inputs (other than growth factors) that contribute to the progression through G1.
High glucose levels and amino acid levels influence early G1 progression.
Describe how DNA damage regulates the cell cycle.
Damage (e.g. radiation) increases the amount of **p53. **
p53 is a transcription factor that arrests the cell cycle -
It blocks (via other molecules) the formation of phosphorylated retinoblastoma gene product, thus blocking G1 from progressing.
Describe the repair of DNA damage.
Mismatch repair genes - e.g. MLH1 gene.
The product of this gene (and many others) helps to recognise and replace DNA base pair mismatches.
MLH1 induces p53 - stopping the cell cycle
Define an oncogene
A mutated gene that can cause cancer, in various ways (e.g. when a growth factor receptor protein has a mutation that means its over expressed.
Pre-mutation = protooncogene
Define a tumour suppressor gene
(Anti-oncogene)
A gene that regulates cell division and when its active, tends to control and even block proto-oncogene)
These can cause cancer when they have mutations (that cause loss of function) or are exposed to environmental factors that inactivate them.
Describe mutations in oncogenes that cause cancer
HER-2 as an example
Mutations can occur that increase the amount of oncogene product.
For instance, a growth factor receptor that is increased in amount is HER-2
Describe mutations in oncogenes that cause cancer
BRAF as an example
Mutations can occur that allow the protein product to work independently of its control mechanism.
For instance, a signal transduction molecule that continues to work all the time (BRAF).
Describe mutations that can occur in tumour suppressor genes that can cause cancer.
Rb
Mutations that can cause the protein product to stop working, e.g. the Rb gene product, if E2F’s are not bound.
Describe how the environment can cause tumour suppressor genes to cause cancer
If a viral protein binds the protein product and stops it working - p53.
Describe how mutations in tumour suppressor genes
MLH1
Mutations can occur taht stop a specific protein working e.g. MLH1 mismatch protein.
