S1: Biology of Cancer Flashcards
What positive signals do cells receive telling it to divide?
Growth factors
Hormones
What is growth factor ‘Epidermal growth factor (EGF)’?
Protein can bind to the cell membrane to its specific receptor (ECF receptor).
Upon binding it will cause signal transduction molecules (secondary messengers) and these will signal to the nucleus where they will cause changes in gene expression
What signal do cells receive telling them not to divide?
-Contact Inhibition: When cell is surrounded by other cells, it receives signals from other cells telling it new cells aren’t needed so it shouldn’t divide
DNA damage response: If there is something wrong with DNA in the cell, the cell will not divide until that DNA is repaired
What does germline mutation mean?
- Present in the fertilised egg
- Present in every cell in the body
- Can be inherited from a parent
- Can be passed to offspring
What does somatic mutation mean?
- Occurs after division of the fertilised egg
- Only present in a subset of cells
- Not inherited from a parent
- Occasionally passed to offspring
Why is cancer called ‘clonal disease’?
It arises from a single cell. This cell has undergone mutations and gene dysregulation so its cell division is no longer tightly controlled
What type of mutations is cancer mostly caused by?
Somatic mutations - Mutations in a single cell rather than inherited mutations
What are the genes that are mutated?
- Oncogenes
- Tumour suppressor genes
What is dominant oncogenes?
With these, only one copy of the gene (one allele in a diploid cell) needs to be mutated
Explain how tumour suppressor genes (TSGs) cause cancer
Tumour suppressor genes (TSGs) require both copies of the gene (both alleles, in a diploid cell) to be inactivated in order to allow cancer to develop.
Typical TSGs may be: cell cycle checkpoint genes, DNA repair genes or genes regulating cell death.
How many mutations cause cancer?
Multiple mutations in different genes are what causes cancer. When one cell acquires enough mutations it begins to grow out of control.
What are the types of cellular genes mutated in cancer?
- Growth promoting genes (which would be dominant oncogenes)
- Cell cycle checkpoint genes and DNA repair genes (which would be tumour suppressor genes)
- Genes regulating cell death (dominant oncogenes or tumour suppressor genes)
How are oncogenes made?
Most oncogenes start out as normal cellular genes coding for a protein carrying out a normal cellular function. They only become an oncogene after genetic alteration. A “proto-oncogene” is a normal gene that can be mutated to become an oncogene.
Example of an Oncogene
HER2 in some cases of breast cancer
Example of tumour suppressor genes
TP53 gene codes for the p53 protein
Explain how DNA repair genes can cause cancer
Many tumours lack proper DNA repair, due to the genes coding for DNA repair proteins being mutated. Hence other genes are more likely to mutate and the cell is more likely to become cancerous.
Mutations in DNA repair genes=Increased risk of mutations in oncogenes/tumour suppressor genes
Give and example of a DNA repair gene
BRCA1
If mutated, individuals are more likely to get breast cancer
How do tumour progress?
- To promote invasion and metastasis
- To become invisible to the immune system
- To induce growth of blood vessels
Why is angiogenesis important for cancer?
Angiogenesis is the formation of blood vessels, for a tumour to grow it must have a blood supply. Cancer cells secrete angiogenic factors to induce new blood vessels. Anti-angiogenic drugs inhibit the growth of tumours.
What is knudsons two hit hypothesis?
SPORADIC
- Single tumour
- Unilateral
- Late onset
HEREDITARY
- Multiple tumours
- Bilateral
- Early onset
What is epigenetics?
Epigenetics is the study of changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.
Give an example of epigenetic modification
DNA methylation
e.g. methylation of cytosine