Flashcards in MOD 21 - Carcinogenesis: molecular hallmarks of cancer cells Deck (31):
what are the 2 key concepts for carcinogenesis?
oncogenes activation & tumour suppressor gene inactivation
what are caretaker genes
maintain genetic stability by repairing damaged DNA and replication errors
what happens to mutated caretaker genes
cause genomic instability - which enable specific genetic alterations to accumulate in carcinogenesis
what is the real name of caretaker genes
tumour suppressor genes
what are the different subtypes of tumour suppressor genes
gatekeepers & caretakers
what does gatekeeprs do?
regulating normal growth
-ve regulators for cell cycle and proliferation, +ve regulator of apoptosis & cell differentiation
what does caretakers do?
maintain genetic stability
- DNA repaire genes
- controlling accuracy of mitosis
what is 2 hit theory?
inactivation of a TSG requires 2 mutations on each copy of the chromosome - first hit is normally a point mutation
who will already have the first hit of the 2 hit theory
ppl with FH ie familial cancer syndromes
what is proto-oncogenes
potential oncogenes which requires only a few mutation to become oncogenes
what can proto-oncogenes do?
promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis
what can mutation of the oncogenes lead to?
activated versions of increased expression of proto-oncogenes - gain of function
how many copies of mutated oncogenes is required to cause damage
only one copy - mutated genes is dominant to other normal parental gene`
what are the 3 different mechanisms which can activate oncogenes
translocation of a proto-oncogenes (from a low transciptionally active site to a higher active sites - aberrant expresison of oncogenes
point mutation - cause hyperactive of the a.acid
ampllification - insert of multiple copies of oncogenes
what does tumorigenesis involve
multi-step process - involves activation of oncogenes and inactivation of TSG
what are the hallmarks of cancer cells
self-sufficency in growth signals, insensitivity to antigrowth signals, tissue invasion and metastasis, limitless potential for replication, sustained angiogenesis, evading apoptosis
how can cancer cells achieve independences in acquiring growth factors
by modifying growth factor receptors and cause them to be over-expressed and activated.
how can cancer cells achieve resistance to -ve growth factor?
retinoblastoma protein (RB) is important regulator as it is inhibited progression of cell cycle and the -ve GF activate the Rb protein and so it will prevent cell cycle
tumour cells will inactivat RB gene and so resistance to -ve growth factors
how come cells have finite replicative lifespan
Due to shortening of chromosome ends (telomeres) after each cell division
what is telomeres
act to prevent end to end fusion of chromosomal DNA molecules
what is telomeres consist of
TTAGG - hexanucleotide sequence repeated thousand times
what happens when the hexanucleotides run out?
Eventually the ends of the chromosomes become exposed and are able to fuse with each other resulting in karyotypic chaos, which usually triggers apoptosis
can telomere be regenerated ?
Telomere regeneration can be accomplished by an enzyme called telomerase
how can tumour cells achieve immortality
Rapidly proliferating tumour cells can overexpress the telomerase enzyme to maintain normal telomere length
what genes involved in apoptosis?
what does P53 do?
induces cell cycle arrest stoping the advancement of cell cycle allowing repair of DNA damage
apoptosis if too much damage
how can tumour cells achieve resistance to apoptosis?
TP53 inactivation - lead to loss of apoptotic response
when does tumour requires its own blood supply
tumours greater than 2 mm in diameter
how does tumour cells achieve angiogenesis?
hypoxia stabilise HIF-1 tanscription factor which induces vascular endothelial growth factor (VEGF) ie recruit endothelial cells that proceed to construct new capillaries and vessels
how is epithelial cells held tightly together
by adhesion molecule E-cadherin - many tumours how loss of this