Lecture 21: Cancer Flashcards
What are carcinomas?
Tumours derived from epithelial cells
What are squamous cell carcinomas?
Tumours arising form epithelial cells that form protective layers
What are adenomas and adenocarcinomas?
Tumours arising from secretory epithelial cells
What is the difference between adenomas and adenocarcinomas?
Adenomas are benign Adenocarcinomas are malignant
What is the process of cancer development?
- Normal epithelium
- Hyperplastic epithelium
- Adenomas which are benign
- Carcinomas which are malignant
- Invasion and metastasis
What are the 10 hallmarks of cancer?
Sustaining proliferative signalling
Evading growth suppressors
Avoiding immune destruction
Enabling replicative immortality
Tumour promoting inflammation
Activation invasion and metastasis
Inducing angiogenesis
Genome instability and mutation
Resisting cell death
Deregulating cellular energetics
How do cancer cells get their hallmarks?
Mutations in oncogenes and tumour suppressor genes
How do genetic mutations go on to disrupt tissue homeostasis?
- Mutated genes
- Altered gene expression profiles
- Dysfunctional protein networks
- Abnormal cell function
- Loss of tissue homeostasis
How do retroviruses work?
- RNA genomes are converted to DNA by reverse transcription
- DNA integrates into host chromosomes and new viral genomes can be synthesised
- V-src is responsible for turning normal cells into cancer cells
What is meant by an oncogene?
A gene with the potential to cause cancer
What was the first oncogene to be disovered?
v-src
What is Ras?
Viral oncogene
Cellular cancer causing gene
What is sporadic retinoblastima?
No family history
One eye
Low risk of other tumours
What is familial retinoblastoma?
Family history
Both eyes
High risk of other tumours
What does the retinoblastoma protein act as?
A tumour suppressor gene
How does RB regulate the cell cycle?
- Inhibits transcription factor E2F
- When active Rb binds to E2F to prevent cell cycle progression
- If Rb is absent E2F is always active and drives entry into S phase even in absence of mitogens
What is neurofibromatosis?
Familial cancer syndrome caused by NF1 mutations
Causes Ras to be constitutively active
What results from a mutation of the Wnt pathway?
Colon cancer
Why is Wnt signalling needed in the crypt?
Maintaining intestinal cell populations
Regulating proliferation and differentiation
What occurs if wnt signals are out of range in normal cells?
B-catenin is off
Cyclin D1 is off
Stop proliferating and differentiate
Migrate up and out
What occurs if the wnt signals are in range?
B catenin is on
Cyclin D1 is on
Proliferation
What occurs if the wnt signals are out of range in cancer?
Bcatenin remains on Cyclin d1 remains on
Keep proliferating without differentiating and remain there
Causes cancer
How does TGF beta signalling act as an inhibitory pathway?
TGF-B signalling brakes the cell cycle
It is a tumour suppressor
If it mutates it can cause cancer
How can Ras cause cancer?
If a single Ras allele is mutated the downstream pathway can get stuck on
This causes continuous growth and causes cancer to grow
