Cell Cycles Dysregulation Flashcards
Why do cells divide?
- Repair/replace cells because of tissue damage and cell death
- Reproduction/Development
- Growth
What triggers cell division?
Mitogens, chemical substances which encourage a cell to commence cell division, lkeading to mitosis e.g. EGF, FGF, VEGF or small moelcules e.g. ATP
These mitogens bind to cell surface receptors and trigger intracellular signalling promoting their entry into the cell
What are the steps of the eukaryotic cell cycle?
Interphase and Mitosis:
Interphase divided into - G1 (Growth) phase , S phase (DNA synthesis), G2 phase (preparation for mitosis) and includes checkpoints to make sure the DNA has doubled and the environment is preferable
Why does proliferation need to be regulated?
Uncontrolled proliferation leads to cancer which is a group of diseases involving abnormal cell growth with potential to invade or spread to other parts of the body
How does cancer develop?
Mutation of mitogen receptor, mutations of intracellular cascade proteins involved in inducing/stopping proliferation, or cell cycle mutations (Phase or Checkpoint mutations)
Why do mutations cause dysregulaion?
Mutation results in a conformational change in the protein, meaning it has impaired/no biological function
What are the causes of mutations?
Multiple causes:
1. UV light/ X-Rays
2. Viruses
3. Bacteria
4. Errors in DNA replication
5. Deletions/insertions
6. Chromosomal translocation
7. Chemicals
8. Radiation
9. Free radicals
What is carcinogenesis and how does it occur?
Carcinogenesis is defined as the formation of cancer - however, cancer does not occur from one mutation it must be multiple mutations and the type of cancer depends how many mutations are needed to form that cancer e.g. kidney cancer = 2 mutations but colon cancer = 11 mutations
What genes are responsible for regulation of proliferation? How do mutations in these genes cause cancer?
Tumour suppresor genes (anti-oncogenes) - Stop cell from proliferating out of control
Proto-oncogenes / Oncogenes - Gene with potential to cause cancer. Either promote growth, inhibit apoptosis or both
Must both mutate to cause cancer
What does formation of an oncogene cause?
Increased cell activity and loss of regulation as well as increased protein expression
What is the role of an anti-oncogene and what does a mutation cause?
Prevention of cell cycle progression and induce apoptosis normally
Mutation = loss of protein or reduced activity resulting in unregulated cell proliferation
These mutations are usually recessive
What is the normal role of p53 in cell cycle regulation? What happens when p53 mutates?
p53 is a normal component of the G1 checkpoint and if DNA damage is detected p53 levels increase and cessation of the cell cyle occurs until the cell is repaired or killed
Mutation = cells proliferate with damaged DNA and avoid apoptosis meaning mutant cells survive and replicate
This is a loss of function mutation and occurs in more than 50% of cancers
What are the main properties of cancer cells?
- Evade apoptosis
- Tissue invasion and metastasis
- Overcome replicative senescence
- Angiogenesis
How do cancer cells overcome cell senescence?
Express telomerase adding telomeres back to the end of chromosomes therefore cells do not become senescent
How do cancer cells recruit their own vasculature? (Angiogenesis)
Cancer cells secrete VEGF which promotes the growth of blood vessels towards the cancer cells (tumour)
