MOD 21 - Carcinogenesis: molecular hallmarks of cancer cells Flashcards Preview

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Flashcards in MOD 21 - Carcinogenesis: molecular hallmarks of cancer cells Deck (31):
1

what are the 2 key concepts for carcinogenesis?

oncogenes activation & tumour suppressor gene inactivation

2

what are caretaker genes

maintain genetic stability by repairing damaged DNA and replication errors

3

what happens to mutated caretaker genes

cause genomic instability - which enable specific genetic alterations to accumulate in carcinogenesis

4

what is the real name of caretaker genes

tumour suppressor genes

5

what are the different subtypes of tumour suppressor genes

gatekeepers & caretakers

6

what does gatekeeprs do?

regulating normal growth
-ve regulators for cell cycle and proliferation, +ve regulator of apoptosis & cell differentiation

7

what does caretakers do?

maintain genetic stability
- DNA repaire genes
- controlling accuracy of mitosis

8

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

9

who will already have the first hit of the 2 hit theory

ppl with FH ie familial cancer syndromes

10

what is proto-oncogenes

potential oncogenes which requires only a few mutation to become oncogenes

11

what can proto-oncogenes do?

promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis

12

what can mutation of the oncogenes lead to?

activated versions of increased expression of proto-oncogenes - gain of function

13

how many copies of mutated oncogenes is required to cause damage

only one copy - mutated genes is dominant to other normal parental gene`

14

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

15

what does tumorigenesis involve

multi-step process - involves activation of oncogenes and inactivation of TSG

16

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

17

how can cancer cells achieve independences in acquiring growth factors

by modifying growth factor receptors and cause them to be over-expressed and activated.

18

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

19

how come cells have finite replicative lifespan

Due to shortening of chromosome ends (telomeres) after each cell division

20

what is telomeres

act to prevent end to end fusion of chromosomal DNA molecules

21

what is telomeres consist of

TTAGG - hexanucleotide sequence repeated thousand times

22

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

23

can telomere be regenerated ?

Telomere regeneration can be accomplished by an enzyme called telomerase

24

how can tumour cells achieve immortality

Rapidly proliferating tumour cells can overexpress the telomerase enzyme to maintain normal telomere length

25

what genes involved in apoptosis?

TP53

26

what does P53 do?

induces cell cycle arrest stoping the advancement of cell cycle allowing repair of DNA damage

apoptosis if too much damage

27

how can tumour cells achieve resistance to apoptosis?

TP53 inactivation - lead to loss of apoptotic response

28

when does tumour requires its own blood supply

tumours greater than 2 mm in diameter

29

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

30

how is epithelial cells held tightly together

by adhesion molecule E-cadherin - many tumours how loss of this

31

how does process of invading and metastasis take place

Epithelial cells are held tightly together by adhesion molecule E-cadherin

Many tumours show loss of E-cadherin through mutation/hypermethylation of the gene

Results in epithelial-mesenchymal transition (EMT)

Mesenchymal cells are motile and secrete proteases - allows them to break through basement membrane and invade the underlying stroma

Metastasis involves the spread of malignant cells via the blood/lymphatic system to secondary sites and the formation of secondary tumours