21 - Carcinogenesis - molecular hallmarks Flashcards Preview

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Flashcards in 21 - Carcinogenesis - molecular hallmarks Deck (30):
1

carcinogens generally attack what

the tumour suppressor genes

2

caretaker gene definition

maintain genetic stability by repairing damaged DNA and replication errors

3

gatekeeper definition

play important roles in regulating normal growth

4

negative regulator gatekeeper does

regulator of cell cycle and proliferation

5

positive regulator gatekeeper

regulates apoptosis and cell differentiation

6

carcinogens do what

induce molecular abnormalities in TSGs that cause reduced/lack of protein expression or inactivation i.e. loss of function

7

inactivation of a TSG requires what

two hit hypothesis

8

how can a TSG be activated according to the two hit hypothesis

lost during chromosomal non-disjunction

or gene conversion

or mitotic recombination

9

retinoblastoma gene

RB1

10

li-fraumeni gene

p53

11

familial adenomatous polyposis gene

APC

12

HNPCC gene

hMLH1, hMSH2

13

which tumours are caretaker tumours

breast, ovarian
colon/endometrial

14

proto-oncogenes

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

15

oncogenes

mutations lead to activated versions or increased expression of proto-oncogenes - GAIN of function`

16

RAS - what is it

commonest oncoprotein

member of guanine nucleotide binding proteins called G-proteins

17

RAS - problems

acquired a GTP molecule and shifted into an active state and unable to an inactive state.

18

RB protein

retinoblastoma protein

19

RB protein - what does it do?

non-proliferating cells behind here and suppresses activity.

may be epigenetically silenced

20

immortal tumour cells

cells have a finite replicative life span as after numerous divisions they die due to loss of DNA from the telomeres. Tumours cells express telomerase that replaces this and they become immortal.

21

TP53 involved with

apoptosis mainly

codes for transcription factor that induces transcription for >100 genes.

22

most common genetic abnormality in human tumours

TP53 mutation

23

TP53 mutation disease

Li-Fraumeni

24

Angiogenesis in tumours

>2mm require a good blood supply
VEGF induced by tumours - angiogenic factor.

25

VEGF stands for

vascular endothelial growth factor

26

E-cadherin

holds epithelial cells together

27

tumours and E-cadherin

show loss of E-cadherin through mutation / hypermethylation of the gene... results in EMT

28

what does EMT stand for

epithelial-mesenchymal transition

29

Herceptin targets

targets HER2

30

What does HER2 gene do?

codes for +ve growth factor receptor which is overexpressed in 30% of breast tumours