Cancer Biology

Question 1

what happens to a cell to grow in an uncontrolled manner?

Answer 1

uncontrolled cell proliferation/growth, blocked differentiation, increased cell motility, acquired cell tissue invasion, genomic stability loss

Question 2

explain the multistep development of tumerogenesis

Answer 2

initiation - result of environmental carcinogen (radiaton, viral)
mutation accumulation - some activates oncogenes and others remove TSGs
further mutations - capabilities to become malignant

Question 3

name the 6 characterisics of cancer cells

Answer 3

cells proliferate in growth signal absense
lose growth inhibitory signals
evasion of programmed cell death
limitless replication potential
sustained ontogenesis
tissue invasion/metastasis

Question 4

explain the steps in a signal resulting in a cell response

Answer 4

extracellular signal, detected by receptors, cytoplasmic signalling intermediates (transducers), signal sent to nucleus, transcription and molecule production for cell response

Question 5

what are oncogenes and proto-oncogenes?

Answer 5

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

Question 6

how does unregulated cell proliferation occur?

Answer 6

molecules which speed up proliferation are turned on (and vice versa)

Question 7

name proto-oncogenes that, if mutated, continue to tumour progression

Answer 7

HER2, Ras, Abl (kinase), Myc, cyclin-D

Question 8

how does a deletion/point mutation result in oncogene formation?

Answer 8

causes hyperactive protein in normal or excessive amounts

Question 9

how does a regulatory mutation or gene amplification result in oncogene formation?

Answer 9

normal protein greatly overproduced

Question 10

name 2 ways a chromosome rearrangement can cause oncogene formation

Answer 10

nearby regulatory DNA sequence causes normal protein to be overproduced

fusion to actively transcribed gene produces hyperactive fusion protein

Question 11

explain RAS and how a point mutation affects it

Answer 11

RAS - G-protein that transduces signals from cells
point mutation - hyperactive RAS constantly active

Question 12

explain BRAF and how a point mutation affects it

Answer 12

BRAF - signal transducing kinase from cell surface receptors
point mutation - hyperactive BRAF constantly active

Question 13

explain EGFR and how a deletion of extracellular portion affects it

Answer 13

EGFR - cell surface receptor receiving extracellular signals
deletion - active in EGF absense

Question 14

name 3 examples of chromosomal rearrangement mutations fusing genes

Answer 14

bcr (chr 22) and abl (chr 9), the philadelphia translocation

Question 15

what is the 2 hit hypothesis?

Answer 15

2 seperate mutational events must occur for retinoblastoma to result in tumourogenesis
(RB - cell cycle gatekeeper)

Question 16

explain how different mutations in p53 result in different cancer formation

Answer 16

germline mutations - li-fraumeni syndrome
somatic mutations - seen in alot of colo-rectic, breast, lung tumours

Question 17

explain the intrinsic process of apoptosis

Answer 17

bcl-2 inhibits apoptosis, in cancerous cells bcl-2 is overexpressed

Question 18

explain how cells are limited in cell replications, and how cancer cells avoid this

Answer 18

cells are limited by telomere shortening
telomeres are added to chromosomes by telomerase, which is reactivated in many cancers

Question 19

explain how tumour cells can grow in size

Answer 19

tumour cells induce blood vessel formation through angiogenesis, when tumour cells become hypoxic they produce VEGF which induces vessels to grow towards tumour

Question 20

explain how tumours metastasise

Answer 20

cells in primary tumours break from eachother, move through BM, move in and out of circulation and attach and grow on new tissue

Question 21

explain how E-cadherin contributes to tumour metastasis

Answer 21

cell junctions are joined by E-cadherin, tumour cells reduce E-cadherin to break off from tumour easier

Question 22

explain how tumours breach the BM

Answer 22

proteases produced (MMPs), degrade the environment allowing the tumour cells to move through it
MMP8 breaks down collagen