Week 3 Flashcards
What is oncogenes and causes of it?
-mutated gene, has the potential to cause cancer
Cause of oncogene:
- Virus
- Chemicals
- Radiation
Explain what the Rous Sarcoma Virus is
It is a retrovirus ( any of a group of RNA viruses which insert a DNA copy of their genome into the host cell in order to replicate)
Gene v-src
- Involved in regulation of cell growth and differentiation
- Not needed for viral replication, but transforms cell leading to cancer
Something in the DNA inserted by the Rous sarcoma virus made the host cells cancerous, but what was it?
- virus picked up a passenger gene called V-src
- V-src was unmistakably similar, but not identical to a gene- C-src- that was discovered in the normal vertebrate genome. C-src had evidently been caught up accidentally by the retrovirus from the genome of a previously infected hostcell, and it had undergone mutation in the process to become an oncogene (V-src)
V-src oncogene
Virus v-src (oncogene, mutated)
- V-src is dominant= only need one copy
- Gain of function
V-src constitutively active tyrosine kinase
- Signalling molecule
- Cannot be regulated
○ Activates kinase signalling cascades
○ Decreased adhesion of cell to surface
○ Growth to high density
○ Loss of contact inhibition
○ Increased transport of metabolites
- Triggers uncontrolled growth
- Original proto-oncogene from vertebrates, cellular src (c-src)
○ C-src expression activated in human tumours
Explain Avian Leukosis virus
Cancer caused by a different mechanism from Rous
- Oncogene
Inserts viral DNA into host genome next to a proto-oncogene
- C-myc (DNA- binding protein) > transcription factor
Viral DNA
- Long tandem repeat sequences
○ Act as strong promoters or enhancers
○ Induces increased expression of c-myc
Receptors
What receptor and function?
Receptor Tyrosine kinases (RTKs)
- Receptors for growth factors
○ Transmembrane protein, intra- and extra-cellular domains
○ Signal transduction pathway
○ May be defective in cancers
§ Mutations can result in continually active receptors
§ i.e. Receptor activity in absence of ligand
Defective receptor tyrosine kinases:
- Erb-B family
○ Her2 (aka ErbB2= 25% of breast tumors)
Function
- Tyrosine kinase domains
- Binding of ligand > phosphorylation of tyrosine
○ Phosphorylate other intracellular signalling proteins
What is Erb-B
- Family of receptor tyrosine kinases related to epidermal growth factor receptor
○ Name derived from viral oncogene: erthyroblastic leukemia viral oncogene - When extracellular domain is missing
○ Receptor is always switch on….
= Uncontrolled growth
What is P53 (tumour suppressor)
- Regulates cell cycle
- Activates other transcription factors
- DNA binding site
- Recognises DNA damage
- “Guardian of the genome”
- can trigger growth arrest, DNA repair, or apoptosis
APC protein ( Adenomatous polyposis coli)
- Tumour supressor protein
- Inhibits myc gene expression
- Myc protein (transcription factor)
Induces expression of many genes required for cell to progress from G1 to S phase - Degradation of beta-catenin
- Beta catenin has 2 roles
- Cell-cell adhesion
- Drives transcription of target genes involved in cell proliferation
- Mutations that activate beta-catenin found in many cancers (oncogene)
APC mutations also cause cancer
- No control of myc or beta-catenin
Colorectal cancer
- Slow developing (over 10-35 years)
- Pre- cancerous growths
- Polyps - form on the inside of colon wall
- Cells in polyp contain mutations in APC gene
- If cells in polyp undergo mutation in Ras
- More uncontrolled cell division
- Another mutation occurs in p53
Malignant carcinoma
three mutations required
Colorectal cancer
- Inherit mutation in one APC gene (Familial adenomatous polyposis)
- Only one more mutation= formation of polyps
- Hereditary disposition to colonic cancer
- 10% cancer patients
- Develop cancer at an early age
- Other patients acquire 2 mutations during their life
Skin
Two types of skin cancer
- Melanoma of the skin
- Starts in melanocytes
- Non-melanoma skin cancer
- Basal cell carcinoma (BCC) and squamous cell carcinoma
Non-melanoma skin cancer (NMSC)
Basal cell carcinoma
- Most often found on head, neck and arms
- Due to exposure to UV radiation
- Leads to formation of thymine dimers, a form of DNA damage
- Basal cells invade the dermis
- Slow growing, usually do not spread
Non-melanoma skin cancer (NMSC)
Squamous cell carcinoma
- Scaly red patches, open sores, warts or elevated growths with a central depression; they may crust or bleed
- Mostly found on head, neck and arms
- Fast growing can spread
Diagnosis
Asymmetry, irregular
Boards (uneven)
Colour ( variegated)
Diameter (greater than 6mm)
Evolving (changing, growing over time)
Characteristics of cancer cells
- Grow continuously
- Lack of control, increased rate
- De-differentiated
- Loss of specialised function
- Lack contact inhibition
-
Altered cell surface characteristics
- Less adhesive
- Invade other tissues
-
Metastasis
- Break through basal lamina and enter circulation
- Secrete a protease > digests basal lamina
Metastasis
- Development of secondary malignant growths at a distance from a primary site of cancer (via blood supply)
- Reduced cell to cell adhesion and cell-matrix adhesion molecules
- Mechanism of metastasis
- If cell-cell or cell-matrix contacts are disrupted
- Tumour cells degrade extracellular matrix and then get between endothelial cells and into capillary
- Cancer cells secrete proteases to digest matrix and establish themselves at new site
- Selectins on endothelial cells recognise carbohydrate groups on cancer cells and allow cancer cells to adhere to endothelial cell at new site in body