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