Cancer Biology Flashcards
what is neoplasm (tumour)?
a new and abnormal growth resulting from autonomous (uncontrolled) cell division
what is a benign tumour?
grow slowly and remain localised to the site of origin
what is a malignant tumour?
invade and spread to different sites = cancer
what does metastasis mean?
it is a multi step process by which tumour cells move from a primary site to colonise a secondary site
oncogene
a gene whose product is involved In inducing cancer. most oncogenes are mutated forms of normal genes (proto-oncogenes) 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. when mutated it becomes a cancer promoting oncogene
tumour suppressor gene
a gene whose encoded protein directly or indirectly inhibits progression through the cell cycle and in which a loss of function mutation is oncogenic
how can the cell cycle and cancer be linked
deregulation of the cell cycle can lead to autonomous and unregulated cell proliferation
what does tumourigenesis mean?
the initial formation of a tumour in the body. a multi step process where a normal cell accumulates a number of alterations or mutations.
what is the initiation of tumourigenesis?
carcinogen exposure eg radiation or chemicals or it can be caused by a virus
what happens after the carcinogen exposure?
the accumulation of many more mutations which can activate oncogenes or inhibit tumour suppressor genes. after the amplification of these mutations due to proliferation one cell passes the threshold to malignency
what does anaplasia mean?
when cells become less differentiated and become less like their tissue of origin.
how can proto oncogenes become oncogenes?
- deletion/ point mutation
- regulatory mutation
- gene amplification
- chromosome rearrangement
deletion/point mutation
hyperactive protein made in normal amounts (eg RAS)
regulatory mutation
normal protein greatly overproduced
gene amplification
normal protein greatly overproduced (ERB B2)
chromosome rearrangment
- nearby regulatory DNA sequence causes normal protein to be overproduced
- fusion to actively transcribed gene produces hyperactive fusion protein with altered function
(eg BCR gene on chr 22 and abl gene on chr 9)
what has a mutation of p53 been linked to?
brain tumours, breast, oesophageal, liver ect. it is the most frequently mutated gene in cancer
what has a mutation on RB been linked to?
retinoblastoma, sarcomas, bladder, breast, lung sarcomas
what has a mutation in BRCA1 been linked to?
breast and ovarian carcinoma
what is apoptosis?
cell death, it is an intrinsic pathway and is an intracellular death signal.
what inhibits apoptosis?
BCL-2 inhibits apoptosis. this can be over expressed and can cause tumour formation or cancer
telomeres
- tandem repeats of hexameter (650-2500 copies)
- prevent end to end fusion of chromosomes
protect chromosome end from degradation - ensure complete replication
- in most human somatic cells telomeres shorten with age
how are telomeres added onto the end of chromosomes?
enzymes called telomerase , this process is amplified in cases of cancers which prevents them for shortening and in turn higher replicative potential
what is angiogenesis
when tumours become too large and far away from blood supply (become hypoxic) they produce VEGF (vascular endothelial growth factor) which makes vessels grow towards the tumour
how can cancer penetrate the basement membrane in order to metastasise?
proteases eg MMP-8 is a protease that degrades collagen
what must a cell do to metastasise?
evade apoptosis, have limitless replication potential, be able to sustain angiogenesis and have tissue invasion capabilities.
What characteristics can be seen on cancer cells?
Large variably shaped nuclei
Many dividing cells
Disorganised arrangement
Variation in size and shape
Loss of normal features
What makes cancer cells appear more blue on a slide?
rRNA and mRNA accumulating in cytoplasm
What is EGF?
(epidermal growth factor) Has many normal functions, for example, proliferation of many different cell types
What is PDGF receptor?
Proto oncogene (platelet derived growth factor receptor)
What is HER2?
Member of EGF receptor family, involved in cell proliferation
What is c-met?
A receptor for growth factor called hepatocyte growth factor
What happens when there is a point mutation on GTPase?
Hyperactive Ras means the cell cycle will no longer need growth factor to enter the cell cycle
Generally what happens during a point mutation?
A dominant effect (making it hyperactive and always switched on)
How is BCL2 gene involved in cancer?
Acts to inhibit/regulates apoptosis, over expressed in cancer cells increasing cells ability to evade apoptosis
How is E- cadherin involved in cancer?
Epithelial tumours often lose it as they progress towards malignancy
What are integrins?
They form part of cell-ECM junctions and are often altered in tumours
what are some features of cancer cell morphology?
-large, variably shaped nuclei
-many dividing cells
-disorganized arrangement
-variation in size and shape
-loss of normal features
what makes cancer cells appear more blue?
as they divide faster, rRNA and mRNA accumulate in the cytoplasm making them more basophilic and appear bluer
what is anaplasia?
when tumour cells become less like their tissue of origin, losing many of their differentiated features
what are some of the new abilities cells gain as they turn into cancer cells?
-uncontrolled cell proliferation
-increased growth capacity
-blocked differentiation
-increased cell motility
-acquireed tissue invasion capability
-loss of genomic stability
what is tumourigenesis?
multi step process where a normal cell accumulates a number of mutations over many years to acquire new characteristics
what is cell motility?
spontaneous movement of a cell from one location to another
what is necrosis?
the death of a body tissue. can be from injury, radiation or chemicals and cannot be reversed.
what are necrotic cells?
uncontrolled cell death that results in the swelling of the cell organelles, plasma membrane ruptures and eventually lysis of the cell.
what is tsg activity?
tissue protective and anti inflammatory processes which cells can lose in tumourigenesis
what is an adenoma?
benign tumour
generally what mutations lead to colon cancer?
K-ras oncogene
further mutations to p53
result in malignant adenocarcinoma
carcinoma meaning?
generally a type of cancer that starts in the cells that make up the skin or linings of organs
what does cancer result from?
alterations in critical regulatory genes
what happens when Ras protein is mutated?
results in it always being active - Raf
what are some examples of proto-oncogenes?
EGFR
HER2
C-MET
Ras
BRAF
some kinases
cyclin D
Myc
what is Ras?
a family of small GTPase that activate kinases in the MAP kinase pathway
what is BRAF?
a kinase in the MAP kinase pathway
what are Src and Abl?
kinases that participate in transducing signals involved in cell proliferation
what are Myc Fos and Jun?
nuclear proteins that are involved in the synthesis of molecules such as cyclin D for cell proliferation
what are TSGs?
normal function is to inhibit cell proliferation and tumour development. in many tumours these genes are lost or inactivated
what is the two hit hypothesis?
at least two mutational events must occur at the same location to result in tumourigenesis. the first must occur in the germ line and the second in a somatic cell
how does p53 function as a tetramer making it unregulated cell proliferation?
only when 4 good monuments combine do they form functional p53. so mixing and matching go monomers mean that even good monomers are prevented from functioning properly. the bad allele will dominate over the good one.
what are telomeres?
sequences on the end of chromosomes which protect the chromosomal ends from degradation and they shorten with age. they also prevent end to end fusion of chromosomes and ensure complete replication
which enzyme regulates the addition of telomeres?
telomerase
which types of cell junctions are often associated with cancer?
-E-cadherins
-cell-ECM junctions
What is MMP5?
Protease which breaks down collagen. Allows ECM to be broken down and allows metastisis
