What is cancer? Flashcards
Define Oncogene and what are the 5 categories of it
Oncogene: gene tha encodes protein capable of inducing cancer
Proto-oncogene: normal gene from which oncogene is derived from. Usually encodes key cell functions
- Growth Factors
- Growth Factors receptors
- Cell signalling molecules
- transcription factors
- pro-/anti-apoptotic proteins balance
Give 3 examples of a growth factor oncogene mutation causing cancer
- Benign Prostate hyperplasia (BPH) - Vascular endothelial growth factor (VEGF)
- angiogenesis
- potent mitogen for endothelial cells - Glioblastoma- platelet derived growth factor (PDGF)
- cellular differentiation & response to tissue damage - Oesophageal cancer- Transforming growth factor alpha (TGFa)
HER2/ErbB2 mutation is an example of?
Growth factor receptor proto-oncogene mutation - overexpression
HER2/ErbB2: epidermal growth factor receptor (tyrosine kinase receptor)
Breast cancer
What are k-Ras and its implication when overexpressed
Proto-oncogene
Ras family: signal transduction protein
Small G-protein
acts as ON/OFF switch for 1) cell division 2) cell differentiation 3) cell survival
Mutated forms
- Glysine (61) -> Lysine: cannot hydrolyse GTP
- Glycine (12) -> Valine: insensitive to inactivation
What are the mechanisms (name 5) by which oncogene arises
These mechanisms can be grouped into five basic categories:
(1) Point mutation,
(2) Gene amplification,
(3) Chromosomal translocation,
(4) DNA rearrangement, and
(5) Insertional mutagenesis.
Give an example of point mutation of proto-oncogene
K-Ras
- Glysine (61) -> Lysine: cannot hydrolyse GTP
- Glycine (12) -> Valine: insensitive to inactivation
What is c-myc as an oncogene?
Transcription factors
amplified in 50% of cancers
promotes transcription of CYCLIN genes (cell cycle progression)
- Burkitt’s Lymphoma (non-hodgkins) -> c-myc translocation
- Breast/colon/Lung cancer -> c-myc overexpression
What mutation is commonly found in:
- leukaemias (all acute lymphocytic lymphoma)
- Non-Hodgkins Lymphoma (around 90% in follicular lymphoma)
- Solid cancer (eg. small cell lung cancer)
Apoptotic and anti-apoptotic proteins mutation
Bcl-2 (anti-apoptotic) vs BAX (apoptotic) balance
- Gain of function: OVEREXPRESSION of Bcl-2
- leads to survival of mutated cells - Loss of function: BAX is activated by p53
Loss of p53 function means cell does not undergo apoptosis when it’s damaged
What are the 2 categories of tumour suppressor genes and give an example each
- Cell cycle control proteins
- p53
- pRB > retinoblastoma - DNA repair proteins
- BRCA1/2 > Breast cancer
What are tumour suppressor genes
gene that encodes from protein capable of blocking the development of cancer
- usually inhibitory genes
Loss of function mutation in cancer
Which cell cycle stage does pRB affect
pRB
no activation of cell arrest
1) Inhibits S phase entry (stops G1 –> S)
2)activated by P53 when damaged DNA is detected, ultimately inhibiting CDK2 and thus S phase entry
What are the checkpoints in a cell cycle?
- G1/S-phase checkpoint
DNA damage + External factors (eg. growth factors)
Cyclin D- CDK4-CDK6 complex activation (phosphorylation) - G2/M-phase checkpoint
DNA damage
cyclin B-CDK1 required to proceed - Metaphase checkpoint
spindle check
Blocked: chromatids not assembled properly on spindle
Give 2 example of caretaker genes (DNA repair proteins)
- BRCA1/2 (DNA repair protein)
2. MMR (mismatched repair protein)
Name 7 features of cancer
a. Unregulated cell cycle- has its own growth signals
b. Unresponsive to anti-growth signals
c. Angiogenesis (formation of blood vessels near tumor to provide nutrients)
d. No apoptosis (immortal)
e. Can metastasize
f. DNA repair impaired
Impaired ability to differentiate
What cell cycle stage does p53 affect?
p53
no inhibition of s-phase gene
1) Halt cell at G1/S phase: Stops cell cycle by activating p21 which inhibits CDK2-cyclin E > cell cannot procede to S-phase
2) Stops cell cycle at G2/M phase (via p21)
3) can activate DNA repair proteins when DNA has sustained damage + initiate apoptosis
4) Essentially helps stop damage cells from dividing
Mutation/dysfunction=excess division=cancer
