L21- Carcinogenesis: molecular hallmarks of cancer cells  Flashcards Preview

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Flashcards in L21- Carcinogenesis: molecular hallmarks of cancer cells  Deck (24):
1

What do Caretaker genes do:

maintain genetic stability by repairing damaged DNA and replication errors

If these get mutated --- > Genetic instability is a common feature of most tumour cells

2

What are gatekeeper genes?

-play important roles in regulating normal growth:

-Negative regulators of the cell cycle and proliferation

-Positive regulators of apoptosis

-Positive regulators of cell differentiation

3

What do Carcinogens do to TSGs?

Carcinogens induce molecular abnormalities in TSGs

cause reduced/lack of protein expression or inactivation of protein – LOSS OF FUNCTION

4

What gene is affected in Retinoblastoma?

Gene: RB1

Gatekeeper

5

What gene is affected in Li-Fraumeni?

p53

gatekeeper/caretaker

6

What gene is affected in Familial adenomatous polyposis?

APC

Gatekeeper

7

What gene is affected in Familial breast cancer?

BRCA1, BRCA2

Caretaker

8

What gene is affected in Hereditary non-polyposis colorectal cancer?

hMLH1, hMSH2

Caretaker

9

What are Proto-oncogenes ?

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

10

What are Oncogenes?

mutations lead to activated versions or increased expression of proto-oncogenes – GAIN OF FUNCTION

---> inc levels of proliferation, survival, angiogenesis and inhibition of apoptosis

Only 1 copy of the gene needs to be activated to induce a gain of function

11

Mechanisms of oncogene activation : Translocation

Translocation of a proto-oncogene from a low transcriptionally active site to an active site

12

Mechanisms of oncogene activation: Point mutation

substitution of a single base pair can alter an amino acid in the protein causing it to become hyperactive

13

Mechanisms of oncogene activation: Amplification

by insertion of multiple copies of an oncogene – increased expression

14

Multi-step tumorigenesis ...briefly discuss steps leading to a neoplastic cell

activation of oncogenes

inactivation of TSGs

Minimum of 3 genetic alterations are needed to transform a normal cell into a neoplastic cell

15

Do tumour cells need the presence of positive growth factors before dividing?

Tumour cells acquire the ability to grow in the absence of these factors

Tumour cells are also unable to respond to negative growth factors

16

What is the role of the RB (Retinoblastoma protein) gene

key regulator of cell cycle by preventing progression from G1 to S phase

-ve GFs inhibit progression of cell cycle by activating Rb protein

17

What happens to the telomeres of Tumour cell's DNA?

Tumour cells express telomerase that replaces the lost material and cells become immortal

18

Function of p53

P53 induces cell cycle arrest to allow repair of DNA damage

But also induces apoptosis if too much damage

TP53 inactivation leading to loss of apoptotic response is the most common genetic abnormality in human tumours ---> Li-Fraumeni

19

What is angiogenesis?

Generation of new blood channels

vascular endothelial growth factor (VEGF) – an angiogenic factor plays an important role

20

Why do Invasion and metastasis occur?

Many tumours show loss of E-cadherin through mutation/hypermethylation of the gene (epithelial cells are held tightly by this)

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

21

What are clinical applications of tumour markers?

Screening
-Detection of tumour
-Detection of predisposition

Diagnosis
-Identification of type and sub-type

Prognosis
-Certain mutations confer worse survival

Therapy
-Predictive markers for therapeutic response
-Development of targeted drugs or gene therapies

Monitoring
-Response to treatment
-Detecting relapse

22

The Prostate-specific antigen (PSA) marker is useful to diagnose...?

prostate cancer

23

The CA125 serum antigen is a marker useful to diagnose?

ovarian cancer

24

Predictive markers for therapeutic response : HER2

codes for a +ve growth factor receptor

Overexpression found in ~30% of breast tumours (gene amplification)

Herceptin is an antibody drug targeted to HER2 and dampens the effects of an overactive HER2 receptor

Only patients with HER2 overexpression have Herceptin treatment as individuals without overactive HER2 receptors will have no beneficial effect