Growth Control - RS Flashcards
(28 cards)
What controls growth?
Cell lineage (internal control of G1/S transition) External/ diffusible factors Cell-cell/ Cell-ECM interactions
How is apoptosis different than tissue damage or necrosis?
The intracellular contents are not released into the extracellular milieu preventing deleterious effects on neighboring cells or inflammation. Necrosis leads to inflammation (remember my lecture?? ;) … ladies…)
What happens in the absence of trophic factors? Describe the intrinsic pathway: (don’t spend too much time on this)
The cell dies. Needs signals to survive. Pro-apoptotic factor Bad interacts w/ anit-apoptotic proteins Bcl2 and Bclxl inserted into outer mitochondrial membrane. Blocks inhibitory action with Bax leading to release of cyt C. Leads to activation of cystein proteases (caspases) ultimately ending in a proteolytic amplification cascade.
What happens in the absence of trophic factor?
Caspase activation
What happens if trophic factors are present?
Inhibition of caspase actiavtion.
What is terminal differentiation?
Cells stop dividing after a pre-set number of divisions and take on a differential phenotype. They express novel set of genes for specialized function of the cell. (Neurons and cardiac myocytes)
What do the caspases do?
The caspases digest important intracellular structural proteins such as “ the nuclear lamins and cytoskeletal proteins leading to the cells demise “ and fragmentation.
Senescence is an example of what sort of cell control?
It is internal control of G1/S transition. Cells in culture stop dividing after about 50-100 divisions (Hayflick number). They lack telomerase.
What happens when the cell’s telomeres become too short?
It activates p53 which is a p21 cdk inhibitor (blocks cell in G1) leading to senescence. The result of this system is it limits unwanted proliferation and protects cells form replicating incomplete/ unstable chromosomes.
Growth factors promote cell proliferation, what mechanisms do they work by? Can they act locally/ systemically?
Concentration and cell type specific. Yes they can be either/both. Locally think of PDGF. Systemically think of erythropoietin.
What is cell adhesion dependence?
It is another external growth factor. Anchorage-dependent cell growth. Cells will not grow in suspension they need adhesive interactions to proliferate (non cancerous cells)
What is contact inhibition?
Cell-cell interaction. Cell density-dependent growth inhibition. If the cells are touching a lot of other cells they stop proliferating (unless cancerous). Eg. wound repair.
What is cell adhesion to the ECM important for?
It is not just structural it can control cell fate.
What is anchorage dependent cell growth?
Cells expressing the highest number of receptors, and therefore adhering most tightly to the basal lamina are the ones with greater proliferative potential.
Growth control is a balance, what is it a balance of?
Stimulatory and inhibitory signals. E.g. Kinases vs phosphatases. GEFS vs GAPs.
What is different in cancer cells in terms of cell division control signals?
They usually lack: growth factor dependence, anchorage dependence, cell-cell contact inhibition, and do not become senescent.
Most cancers result from mutations affecting the function of proteins involved in important growth regulatory signal transduction pathways. What are the two main classes?
Oncogenes and Tumor suppressor genes
What happens with oncogenes that leads to cancer?
Oncogenes are mutated (or overexpressed) versions of genes normally found in cellular genomes. The normal genes are called Proto-oncogenes
Where were oncogenes first discovered?
In retroviruses - viral oncogenes. e.g. the non-receptor tyrosine kinase, Src was identified as the transforming agent carried by the Rous sarcoma virus (causes skin tumors in poultry). Viruses only 15% of cancers.
What are the more important factors associated with oncogenes (not viruses)?
Genetic and environmental factors are generally more important. Conversion from a proto-oncogene to an oncogene is usually the result of ! somatic mutations (not inherited)
What are proto-oncogenes important for?
Proto-oncogenes are important proteins at all levels of growth control pathways. They are proteins that normally stimulate growth/cell proliferation. Conversion to an oncogene results in elevated and/or unregulated activity. Mutation of a SINGLE allele of a proto-oncogene can cause abnormal growth
What are three potential mechanisms for conversion of proto-oncogenes into oncogenes?
Point mutation in coding sequence leading to hyperactive protein made in normal concentration. Gene amplification overproducing the protein. Chromosome rearrangement and fusion to an actively transcribed gene.
What do tumor suppressor genes function to do?
Tumor suppressor genes normally function to oppose the activity of proto-oncogenes ie. They normally inhibit growth. Cells lose growth control (become transformed) when these genes are mutated to an inactive form.
How can DNA viruses affect tumor suppressor function?
They can interfere with Rb and p53 function by utilizing the host cells to produce proteins normally encoded by the viral genome that bind to and sequester Rb and p53 thereby promoting uncontrolled proliferation.
