Cancer Biology Flashcards
Cancer cell morphology
- large, variable shaped nuclei
- many dividing cells, disorganised arrangement
- variation in size and shape
- loss of normal features
Change from normal cell to cancer cell
- uncontrolled cell proliferation
- increased growth capability
- blocked differentiation
- increased cell motility
- acquired tissue invasion capability
- loss of genomic stability
Development of cancer
- accumulation of mutations in genes
- initiation due to environmental factors
- activation of oncogenes, loss of tumour suppressor
- proliferation increases
- further mutations
- one cell passes threshold to malignancy
Characteristics of cancers
- self- sufficiency in growth signals:
- insensitive growth- inhibited signals:
- evasion of programmed cell death:
- limitless replication potential:
- sustained angiogenesis
- tissue invasion and metastasis
Cell proliferation or behaviour in response to signals
Platelet-derived Growth Factors (PDGF)- matrix formation( increased numbers and activity of fibroblasts), remodelling (production of proteases)
- vascular endothelial growth Factors (VEGF)- angiogenesis
-Colony stimulating factor (CSF) - myeloid lineage in heamatopoiesis
- thrombopoietin- production of platelets
- erythropoietin- production of red blood cells
Oncogene
A a gene whose product is involve in including cancer, most oncogene are mustered form of normals genes involved in the control of cell growth or division
Proto-oncogene
- a normal cellular gene that encodes a protein usually involved in regulation of cell growth and proliferation and when mutated becomes a cancer promoting oncogene
Tumour suppressor gene
- a gene whose encoded protein directly or indirectly inhibits prepress ion through the cell cycle and in which a loss of function mutation is oncogenic
Unregulated cell proliferation: tumours
Extra cellular signal (hormone, peptide growth factors)- receptors ( cell surface receptor, EGFR, HER2, c-MET)- cytoplasmic signalling intermediates ( cytoplasmic molecules, Ras, BRAF, AbL)- nuclear target (nuclear molecules, cyclin d) - cell responses
Gene amplification
- RB B2 (HER2, human epidermal growth factor receptor 2) transmembrane receptor that receives signals from other cells
- amplified in 20% of breast cancers- poor prognosis
Chromosome rearrangement
- nearby regulated FNA sequence cause normal protein to be over produced. Fusion to actively transfigured genes produces hyperactive fusion protein
- bcr gene on chr 22 + abl gene on chr 9 -> Philadelphia translocation = bcr-abl hybrid gene in CML
p53 tumour suppressor
a tetrameric transcription factor “dominant negative”
- germ line mutation pre- disposes to Ali- fraumeni syndrome
- p53 Insctivated in ~50% all human cancers
deletion mutation
- RAS= GTPase that transducer signals from cell surface receptors
-BRAF= kinase that transacts signals from cell surface receptors
-EGFR= cell surface receptor that receives extracellular signal
retinoblastoma tumour supressor
- inherited and sporadic cases of retinoblastoma
- the two hit hypothesis of tumour formation: at least two mutations events must occur at the same locus to result in tumour genesis
