Cancer Cell Biology Flashcards
What is a carcinogen?
A substance capable of causing cancer in living tissue
What are some way carcinogens react with DNA and cause mutations?
Chemically modify bases-point mutation
Strand breaks-deletion, chromosome translocation
What are some causes and risk factors of lung cancer?
Air pollution, asbestos, radon, smoking, second-hand smoking
What is a polyp?
An encapsulated abnormal outgrowth
What is Wnt and where is it produced?
Wnt (Wingless Integrated 1) is a secreted glycoprotein
Produced by the stromal cells at the bottom of the colonic crypts
What is the function of Wnt?
To drive proliferation
It is a growth stimulatory pathway
Explain the wnt signaling pathway?
- Wnt binds to the frizzled receptor
- This causes the phosphorylation of LRP, inducing the translocation of the destruction complex towards the receptor.
- This releases Beta-catenin which translocates into the nucleus and acts as a transcription factor (increased cell prolideration)
Explain what happens in the absense of the wnt signaling pathway?
- Wnt dosent bind
- Destruction complex remains together and activates
- GSK-3 phospharylates Beta-catenin
- Beta-catenin undergoes ubiquitination and breaks down ( inhibition of proliferation)
What is the destruction complex in the wnt signalling pathway made up of?
GSK-3
Axin
Beta-catenin
APC
How does the mutation of APC in the destruction complex lead to cancer?
- loss of function of APC prevents the ubiquination and degredation of the Beta-catenin
- So can function as transcription factor and increase cell proliferation
What is meant by the multi-steps of cancer?
That it is a series of mutations and not just one
Starts off as a small adenoma, then leads to a large adenoma and then cancer
What is sporadic cancer?
Cancer due to a random chance/enviromental exposure
-accounts for around 70% of cancers
What is familial cancer?
Cancer that occurs in families
-from shared enivromental exposure
-similar genetic background
Accounts for around 20% of cancers
What is hereditary cancer?
Cancer due to a inherited genetic mutation
Increased risk of cancer development
-Accounts for around 10% of cancers
What are the 3 main categories of cancer?
Sporadic
Familial
Hereditary
What do the hallmarks of cancer represent?
They outline the possible biological capabilities that can be aquired during the multistep process of cancer development
What is clonal evolultion in cancer?
Where with each mutation the abnormal cell gains selective advantage (heterogeneity) over neighboring cells giving rise to a clonal population
What is tumour heterogeneity?
The observation that different tumour cells can show different mutations and morphological profiles
What are cancer critical genes?
All genes whose mutation contributes to the causation of cancer
What are the 2 main classes of cancer critical genes?
Proto-oncogenes
Tumour suppressor genes
What are proto-oncogenes?
Normal genes within our cells that promtoes cellular proliferation
-the accelerator
What occurs when a proto-oncogene mutates?
Proto-oncogenes when mutated, become over activated or overexpressed
- become an oncogene
- leads to increased/uncontrolled proliferation
What are the 3 mechanisms that produce oncogenes?
Translocation -new promoter region
Gene amplification-multiple copies
Mutation- within control region or within the gene
What is the Philadelphia chromosome?
A changed chromosome 22, containing part of chromosome 9 (reciprocal translocation)
What is the other name for the Philadelphia chromosome?
The BCR-Abl fusion gene
What does the Philadelphia chromosome cause?
Produces increased levels of tyrosine kinase activity
-leads to increased cell proliferation
What cancers is the Philadelphia chromosome found in?
Found in Chronic Myeloid Leukaemia (CML)
And in Acute Lymphoblastic Leukaemia (ALL)
Are oncogenes dominant or recessive?
Dominant
What is the significance of oncogenes being dominant?
There only need to be a mutation in one of the alleles to produce the uncontrolled cell growth
-higher chance of loss of function
What are tumour suppressor genes?
Normal genes that negatively regulate (supress) cell proliferation
-the brakes
What occurs when a tumour supressor gene mutates?
Results in a loss of function of the corresponding protein
Cell proliferation not regulated- leads to uncontrollable cell proliferation
Is a tumour suppressor gene usually dominant or recessive?
Recessive
What is the significance of a tumour suppressor gene being recessive?
A mutation in one allele doesn’t result in a loss of function
Loss of function requires a mutation in both alleles
-less chance of loss of function
What is retinoblastoma and how is it caused?
The most common eye cancer in children
-caused by the mutation of the retinoblastoma (Rb) gene
What theory did Knudson propose?
The 2 hit hypothesis ( the Knudson hypothesis)
What is the 2 hit hypothesis?
That most tumour supressor genes require both alleles to be inactivated, either through mutation or epigenetic silencing, to cause a phenotypic change
What are the different mechansims of how a tumour suppressor gene can be inactivated?
-Epigenetic silencing
-deletion of both alleles- homozygous deletion
-loss of function to both alleles
-loss of function to one allele and deletion of another
(loss of heterozygosity)
What is a germline mutation?
A germline mutation is mutations in germ cells (reproductive cell in the body). These mutations are the only mutations that can be passed to offspring
What is a germ cell?
A germ cell is a reproductive cell of the body. Found in egg cells of females and sperm cells of males
What are examples of a germline mutation?
Retinoblastoma (Rb gene) Breast/Ovary cancer ( BRAC1 and BRAC2 gene) Colorectal cancer (APC)
What are the different types of point mutation?
Silent
Missense
Nonsense
What is a silent point mutation?
Change in single base
- same amino acid coded for, dosen’t affect the function of the protein
What is a missense point mutation?
Change in single base
-results in a codon that codes for a different amino acids therefore could or could not affect function of protein
What is a nonsense mutation?
Change in base that produces a stop codon
- stops transcription of protein therefore changes the fucntion of that protein
