wk 1.2 intro to onco and tumour suppressor genes

Question 1

hallmarks of cancer

Answer 1

• autonomous proliferative signalling often caused by activated oncogenes
• inhibition of growth inhibitory signals (loss of tumour suppressor genes)
• evasion of programmed cell death
• immortalisation of a malignant cell
• tumour angiogenesis
• tumour metabolism
• evasion of the immune system
• acquisition of the ability to invade neigbouring tissue and metastasise

NB: can occur in any order accept the last one

Question 2

what are proto-oncogenes

Answer 2

also known as cellular oncogenes they are genes that regulate normal cell growth and survival

Question 3

what are oncogenes

Answer 3

they are proto-oncogenes that have mutated and now code for proteins that stimulate uncontrolled growth and promote cell survival

-they are dominant and their expression only requires a single mutant allele

Question 4

how do proto-oncogenes control cell growth

Answer 4

they encode key regulatory proteins:

• proliferative signalling pathways
• cell death signalling pathways
• cell cycle signalling pathways

Question 5

what are the functional classes of proto-oncoproteins

Answer 5

1. growth factor /prolifirative pathway ligands
2. Growth Factor Receptor (RTK)

signal transducers (proteins which transmit the signal through the cytoplasm):

3. monomeric guanosine-binding protein
4. non receptor kinases: proteins that phosphorylate substrate proteins
5. transcription factors
6. apoptosis associated proteins

Question 6

1. growth factors/proliferative pathway ligands

Answer 6

polypeptides produced by tumour cells signal in autocrine loops stimulating tumour cell proliferation (PDGF, HGF,VEGF,WNT,IL8)

Question 7

2. growth factor receptor (RTK)

Answer 7

transmits information in a unidirectional manner across the cell membrane;
binding growth factor / cytokine to its receptor activates receptor tyrosine kinase activity. (EGF receptor,KIT,FLT3)

Question 8

3.monomeric guanosine-binding proteins

Answer 8

Regulate by either binding to GDP or GTP (RAS)`

Question 9

4. non receptor kinase

Answer 9

proteins that phosphorylate substrate proteins

• tyrosine kinase: SRC
• serine/threonine kinases: AKT
• Lipid kinase: PI3K

Question 10

5. transcription factors

Answer 10

nuclear proteins that regulate the exppression of genes and gene families resulting in formation of proteins that regulate the cell cycle and cell division (MYC,FOS,JUN, beta CATENIN)

Question 11

6. apoptosis associated proteins

Answer 11

these cells ensure cell survival by interfering with death pathways.
-eg: BCL2
BCL2 levels are increased in many lymphomas. it binds to BAX or BAK preventing mitochondrial pore formation and initiation of the intrinsic pathway of apoptosis

Question 12

mechanisms of oncogene activation

Answer 12

• mutations wich result in a gain of function (eg: a protein that is cunstitutively active is formed
• gene amplification (over expressed protein)
• translocation
• retroviral activation of a gene
• oncogenes can also be over expressed if the miRNA regulating the degradation of their mRNA is lost or the oncogene losses its miRNA binding point within its UTR

*only one allele needs to ne mutant (dominant)