Cancer Biology Flashcards
what happens to a cell to grow in an uncontrolled manner?
uncontrolled cell proliferation/growth, blocked differentiation, increased cell motility, acquired cell tissue invasion, genomic stability loss
explain the multistep development of tumerogenesis
initiation - result of environmental carcinogen (radiaton, viral)
mutation accumulation - some activates oncogenes and others remove TSGs
further mutations - capabilities to become malignant
name the 6 characterisics of cancer cells
cells proliferate in growth signal absense
lose growth inhibitory signals
evasion of programmed cell death
limitless replication potential
sustained ontogenesis
tissue invasion/metastasis
explain the steps in a signal resulting in a cell response
extracellular signal, detected by receptors, cytoplasmic signalling intermediates (transducers), signal sent to nucleus, transcription and molecule production for cell response
what are oncogenes and proto-oncogenes?
oncogenes - a gene whose product is involved in inducing cancer
proto-oncogenes - a normal gene involved in cell growth/proliferation, which is then mutated to become an oncogene
how does unregulated cell proliferation occur?
molecules which speed up proliferation are turned on (and vice versa)
name proto-oncogenes that, if mutated, continue to tumour progression
HER2, Ras, Abl (kinase), Myc, cyclin-D
how does a deletion/point mutation result in oncogene formation?
causes hyperactive protein in normal or excessive amounts
how does a regulatory mutation or gene amplification result in oncogene formation?
normal protein greatly overproduced
name 2 ways a chromosome rearrangement can cause oncogene formation
nearby regulatory DNA sequence causes normal protein to be overproduced
fusion to actively transcribed gene produces hyperactive fusion protein
explain RAS and how a point mutation affects it
RAS - G-protein that transduces signals from cells
point mutation - hyperactive RAS constantly active
explain BRAF and how a point mutation affects it
BRAF - signal transducing kinase from cell surface receptors
point mutation - hyperactive BRAF constantly active
explain EGFR and how a deletion of extracellular portion affects it
EGFR - cell surface receptor receiving extracellular signals
deletion - active in EGF absense
name 3 examples of chromosomal rearrangement mutations fusing genes
bcr (chr 22) and abl (chr 9), the philadelphia translocation
what is the 2 hit hypothesis?
2 seperate mutational events must occur for retinoblastoma to result in tumourogenesis
(RB - cell cycle gatekeeper)
explain how different mutations in p53 result in different cancer formation
germline mutations - li-fraumeni syndrome
somatic mutations - seen in alot of colo-rectic, breast, lung tumours
explain the intrinsic process of apoptosis
bcl-2 inhibits apoptosis, in cancerous cells bcl-2 is overexpressed
explain how cells are limited in cell replications, and how cancer cells avoid this
cells are limited by telomere shortening
telomeres are added to chromosomes by telomerase, which is reactivated in many cancers
explain how tumour cells can grow in size
tumour cells induce blood vessel formation through angiogenesis, when tumour cells become hypoxic they produce VEGF which induces vessels to grow towards tumour
explain how tumours metastasise
cells in primary tumours break from eachother, move through BM, move in and out of circulation and attach and grow on new tissue
explain how E-cadherin contributes to tumour metastasis
cell junctions are joined by E-cadherin, tumour cells reduce E-cadherin to break off from tumour easier
explain how tumours breach the BM
proteases produced (MMPs), degrade the environment allowing the tumour cells to move through it
MMP8 breaks down collagen
