MOD S7 Flashcards
What does the size of the cell population depend on?
How might a cell population increase in size?
Rate of cell proliferation, differentiation and apoptosis.
Increased numbers seen with:
- Increased proliferation
-Decreased cell death
What regulates cell proliferation under normal conditions?
Proto-oncogenes.
Directly controlled by chemical signals from the microenvironment that stimulate or inhibit proliferation.
Signalling molecule binds to cell surface receptor (sometimes` cytoplasmic or nuclear) and modulation of gene expression occurs.
What are the 4 outcomes of cellular signalling that might influence the size of cell populations?
Survive - resist apoptosis, Divide - enter cell cycle, Differentiate, Die - undergo apoptosis
Cell to cell signalling is achieved by which 3 things?
Hormones, Local mediators, Direct cell to cell stroma contact
What are the 3 modes of signalling? give a brief description of each type
Autocrine:
-Cell produces and secretes a molecule which then acts on surface receptors of the same cell.
-Intracrine is an example but the factors aren’t released from the cell and act on intracellular receptors.
Paracrine:
-Cell produces a signalling molecule which then acts on adjacent cells.
-The responding cells are close to the secreting cell and are often of a different type
Endocrine:
- Molecule produced and secreted, then travels in blood to a distant cell and binds to receptors.
What are growth factors an example of? Give some details about their propertes
Examples of local mediators.
- They are polypeptides that act on specific cell surface receptors.
- Are considered local hormones because they act over a short distance.
- Coded for by proto-oncogenes
- Stimulate (but can inhibit) transcription of genes that regulate entry of a cell into the cell cycle and the cell’s passage through the cycle.
What processes can growth factors effect?
Cell proliferation and inhibition, Locomotion, Contractility, Differentiaion, Liability, Activation and Angiogenesis.
Give some examples of growth factors and their functions
Epidermal growth factor:
- Mitogenic for epithelial cells, hepatocytes and fibroblasts; produced by keratinocytes, macrophages and inflammatory cells; binds to epidermal growth factor receptor (EGFR)
Vascular endothelial growth factor:
- Potent inducer of blood vessel development (vasculogenesis) and role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing.
Platelet derived growth factor:
- Stored in platelet alpha granules and released on platelet activation
-Also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
-Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
Granulocyte colony-stimulating factor:
-Stimulates bone marrow to produce granulocyes, particularly neutrophils, and release them into the blood
What does it mean if something is mitogenic?
It promotes mitosis
When do cells permanently exit the cell cycle? What stage do they enter?
When they have terminally differentiated. G0.
What are the stages of the cell cycle?
What about when cells are not actively proliferating?
Mitosis
Interphase: G1, S, G2
Cell not active in the cell cycle enter G0 after G1
What are quiescent cells?
Inactive cells (usually found in g0)
How can cell behaviour be altered to increase growth of a tissue? (Refer to the cell cycle)
Shortening of the cell cycle
Converting quiescent cells to proliferating cells by making them enter the cell cycle.
What feature of the cell cycle can be seen under a microscope?
Only mitosis and cytokinesis
What are the cell cycle checkpoints and why are the important?
Events where the cell’s DNA is checked for errors before continuing in the cell cycle.
2 important checkpoints at the end of G1 and before M.
Prevent cells with abnormal DNA from passing this onto daughter cell and causing dysfunction/malignancy.
What is p53 known as? Why?
The guardian of the genomes. It mediates apoptosis in response to DNA damage.
What is the restriction point? Where is it found?
It is found at the end of G1 and is the most important checkpoint.
Give some facts about the restriction point:
Majority of cells that pass the R point will complete the cell cycle
It is the the most commonly altered checkpoint in cancer cells
Checkpoint activation delays the cell cycle and either DNA repair mechanism are activated or apoptosis by p53
What are defective cell cycle checkpoints a major cause of?
Genetic instability in cancer cells.
What proteins are responsible for cell cycle regulation?
Cyclins, Cyclin-dependent kinases (CDKs)
Describe cell cycle regulation
Cyclins bind to cyclin-dependent kinases (CDKs) and the cyclin CDK comples.
These phosphorylate proteins that are critical for progression to the next stage (e.g retinoblastoma susceptibility protein)
Cyclin-CDK complexes tightly regulates by CDK inhibitors
Growth factors also involved:
- Some stimulate cyclin production
- Some inhibit CDK inhibitor production
What is the major function of adult stem cells?
- Replenish the loss of differentiated cells while maintaining their own population
- They achieve this through symmetric replication (one daughter cell is a stem cell, one will mature and differentiate)
- Only one mature cell type can be produces (aka lineage specific ) - c.f embryonic stem cells.
What is the difference between labile, stable and permanent cells?
Labile: Cells continue to multiply throughout life
Stable: Cells can multiply in a regenerative burst but are usually quiescent (inactive)
Permanent: cells that cannot proliferate.
Give examples of labile, stable and permanent cell populations
L:
- Surface epithelia (skin and gut epithelia)
- Bone marrow
S:
- Liver hepatocytes
- Bone osteoblasts
P:
- Brain neurones
- Cardiac and skeletal muscle
