Oncogenes, Cell Growth, and Cancer (3)

Question 1

What are the effect of matrix metalloproteinases (MMPs)?

Answer 1

Remove autoinhibitory region of growth factor
Disrupt cell-cell adhesion
Disrupt cell-matrix adhesion

Question 2

Which types of MMPs are overexpressed in malignant growths?

Answer 2

MMP-2 and MMP-9

Question 3

Why are MMPs usually inactive?

Answer 3

Catalytic domain inhibited by propeptide

Question 4

What activates the catalytic domain of MMPs?

Answer 4

Furin protein

Question 5

Describe the process of angiogenesis in metastasis

Answer 5

Cancer cells release VEGF/FGF - detected by endothelial cells at capillary ends - move towards it - neovascularisation of tumour

Question 6

Which molecules stimulate angiogenesis?

Answer 6

VEGF, FGF, EGF, PDGF
Cytokines
Small 2nd messengers - adenosine, prostaglandins

Question 7

What is the effect of the Bel-2 protooncogene?

Answer 7

Inhibits protein cascade - involves PI3K - overexpression of PKB/Akt (threonine kinase) in cancer cells - cell survival

Question 8

In what way does cancer cell metabolism differ from that of normal cells?

Answer 8

Relies on glycolysis

Question 9

What enables increased glycolysis in cancer cells?

Answer 9

Increased M2-PK enzyme

Question 10

What detects the levels of ATP?

Answer 10

mTOR (threonine kinase)

Question 11

What are the properties of transformed cells?

Answer 11

Reduced requirement for growth supplements
Loss of capacity to enter quiescent state
Altered morphology - shiny
Loss of contact inhbition
Loss of anchorage dependence
Form tumours in ‘nude’ mice - lack immune system

Question 12

What is the insensitivity to anti-growth signals in cancer cells caused by?

Answer 12

Loss of Rb (tumour suppressor)

Question 13

What causes tumour regrowth?

Answer 13

Cancer stem cells