Cells and Cancer Flashcards
What are the 6 characteristics of cancer?
Acquire ability to replicate without signals Insensitive to inhibitory growth signals Evasion of apoptosis Limitless replication potential Sustained angiogenesis Tissue invasion
What is autonomous cellular replication?
performing the cell cycle to create 2 daughter cells with no control for environment, stimuli, or inhibitory proteins
What does the Platelet Derived Growth Factor do?
Matrix formation (increased numbers/activity of fibroblasts) Remodelling
What does Vascular Endothelial Growth Factor do?
Promotes Angiogenesis
What does Epidermal Growth Factor do?
Stimulates cellular proliferation (fibroblasts and epithelial cells)
What does thrombopoietin do?
Stimulates platelet formation
What does erythropoietin do?
Produced by kidneys to stimulate erythrocyte production
What does Colony Stimulating Factor do?
Stimulate myeloid lineage in haematopoiesis
How do cells receive stimuli from growth factors?
Receive signal on cell surface, which typically initiates a intracellular cascade initiating production of cyclins.
What colour would a tumour cell stain if haematoxylin and eosin was used and why?
It would be more blue within the cytosol due to higher metabolic activity of the ribosomes and presence of mRNA.
More erratic and blue nucleus
If tumour is larger, it would have presence of disorganized, dark blue nuclei following no particular pattern
What are common proto-oncogene cytoplasmic molecules?
Ras, B-RAF, Abl and Src (kinases)
How can mutations result in proto-oncogenes becoming oncogenes? Touch on types of mutations and their given impact.
deletion/point mutation- hyperactive protein made in normal amounts
regulatory protein mutation- normal protein in overproduced
amplification- overproduction of normal gene products
rearrangement- can move gene to different regulatory sequences resulting in hyper active fusion protein
What are examples of point mutation leading to an oncogene?
Ras- point mutation causes Ras to become hyperactive, dominant feature, found in 30% of tumours
BRAF- a kinase that transduces signals from cell surface, a point mutation results in hyperactive kinase. 50% of melanomas
What is an example of a deletion mutation leading to an oncogene?
EGFR- cell surface receptor, deletion mutation causes deletion of extracellular portion so the receptor is active even when EGF isn’t present
Found in non-small cell lung cancer
What is an example of a Gene amplification mutation leading to an oncogene?
ERB B2 (HER 2, human epidermal growth factor receptor 2) is a transmembrane receptor that receives signals, but is overexpressed in some tumours.
many copies of the protein are produced
found in 20% breast cancer, poor prognosis
What is an example of gene translocation mutation leading to an oncogene?
BCR gene on chromosome 22 is brought together with Abl gene, forming BCR/Abl hybrid.
Hybrid forms a hyperactive tyrosine kinase receptor, causing excessive leukocyte replication (occurs in chronic myeloid leukaemia)
Chromosome called the Philadelphia Chromosome
What are common tumour suppressor genes?
P53
Retinoblastoma
BRCA1
What causes the formation of a p53 related tumour?
Somatic mutation is TP53 (gene that produce p53 protein)
Found in half of all tumours
What is Li-Fraumeni Syndrome?
Inherited mutation of p53 tumour repressor
Increases risk of developing types of tumours
Related to germ line mutations
What process is the BRCA1 gene involved in in terms of its role in halting the cell cycle?
Involved in halting cell cycle for DNA repair
Chronic myeloid leukaemia accounts for 15-20% of adult leukaemia’s. Which molecular defect is associated with CML?
A chromosomal translocation resulting in the bcr-abl fusion
How can cells (mutating into cancers) avoid programmed death?
Increased expression of BCL-2
It inhibits apoptosis by regulating the mitochondrial membrane, therefore constantly inhibiting apoptosis
Inhibition of p53 to prevent stimulation of pro-apoptotic factors
How does the p53 gene initiate apoptosis in a normal cell?
Activates transcription of the Pro-Apoptotic Gene.
Pro-Apoptotic Gene then transcribes Bax
Bax works to create pores in the mitochondrial membrane, allowing for cytochrome C release.
Cytochrome C release then activate caspases (9 then 3).
Caspase 3 can then cause apoptosis of the cell.
What cancers involve BCL-2 translocation?
Lymphomas
How is unlimited cellular replication achieved in cancerous cells?
Hayflick limit is removed in 90% of cancers.
Telomerase enzyme is turned on/ upregulated, and is constantly elongating the telomeres of DNA, allowing for unlimited replication
How do cancer cells enhance their nutrient/oxygen delivery?
Early stages, they receive it via diffusion, but the cancer will grow, and diffusion will not be possible.
They acquire ability to release VEGF, and the hypoxic state of the tumour cells will release it, causing angiogenesis towards the tumour
What abilities does a tumour cell need in order to become metastatic?
Cells need to be able to disassociate from each other, invade basement membrane, migrate to other regions via entry and exit to circulation, and colonize in new location.
