Neoplasm- abnormal mass
disease of the ageing
- enviromental agent exposure
- mutation DNA
- decreased ability of cellular repair-failure of immune system
hallmarks of cancer
- signalling action between cells (autonomy)
- evasion of growth inhibitory signal and cell death
- angiogenesis- formation of new blood vessels
- invasion (metastasis)
growth signal autonomy
- normal cell- external signal to divide
cancer - not dependant on growth factor signalling
- mutations shorten growth factor pathways leading to unregulated growth
- autocrine signalling - cell secretes hormone or chemical messenger that binds to autocrine receptors on that same cell.
- deregulation of receptor firing
evasion of growth inhibitory signals
- normal cell - respond to inhibitory signals to maintain homeostasis
- cancer - no response to inhibitopry signals
- mutations interfere with the inhibitory pathways
cell cycle control
- Cyclin - protiens that control the progression of cells through the cell cycle by activating cell cyclin dependant kinase. (drive cell cyle, regulate transcription and mrna prcessing)
- APC - Anaphase promoiting complex. marks target cell proteins for degredation by 26S proteasome.
- CKI - cyclin dependant kinase inhibitor. blocks kinase activity (G1- phase?) or in response to enviromental signals or DNA damage. Major families: the INK4 family and the CIP/KIP family. The INK4 family proteins are strictly inhibitory and bind CDK monomers.The CIP/KIP family proteins bind both the cyclin and the CDK of a complex and can be inhibitory or activating.
unlimited replicative potential-telomeres
- normal cell - autonomous counting device to define a finite number of cell doublings after which they become senescent (bilogical ageing, deteriation leading to death) this cellular counting device is the shortening of chromosomal ends TELOMERES.
- cancer cells maintian telomere length
- altered regulation of telomere maintenance is unlimited replicative potential
- Repetitive DNA sequences at the ends of chromosomes, protect the end
- human telomeres 250-1500 copies of repeat sequence TTAGGG, each division 50-100bp are lost, progressive shortening with each division. At threshold length cells enter a stable state. if cells bypass this state chromosomal instability results in apoptosis.
unlimited replicative potential - telomerase
- maintain telomere length in some cells
- 85% of tumours show upregulation of telomerase, it transforms normal fibroblasts (extracellular matrix- collagen) to cancer cells IN VITRO (in glass-experimental)
- sevreal oncogenes regulate expression.
Evasion of Apoptosis
- Apoptosis - response to DNA damage
- cancer - evades apop signals, loss of apoptotic regulators
Apoptosis or programmed cell death, is a highly regulated (genetically programmed) process that allows a cell to self-degrade in order for the body to eliminate unwanted or dysfunctional cells.
apoptosis is involved in embryo development and homeostasis. also directly involved in degenerative disease, autoimmune disorders, viral disease and neoplasia (cancer development)
regulators of apoptosis
- p53 - tumour suppressor, protein 53. regulates cell cycle, DNA repair, apoptosis, genomic integrity (consistency of genes)
- Bcl proteins - 20 members - some anti-apoptotic,some pro, bcl2 (b cell leukemia/lymphoma encoded by bcl gene.
- Caspases - 14 identified- cysteine-dependent asparate-specific proteases; homologs of C.elegan…