Do all cells grow at the same rate?
No - there are some cells that divide rapidly (small intestine, epidermis), so slow/never (neurons)
What combination of factors leads to grow control?
1. Cell lineage
2. External/diffusible factors (i.e. growth factors)
3. Cell-cell/cell-ECM interactions
Is apoptosis a normal occurence during development?
Yes! Programmed cell death occurs to prevent syndactyly
Also is result of checkpoint error in DNA replication/cell cycle
Describe the apoptosis in neuronal development
Nerve cell bodies have a 1:1 relationship with Target cells, extraneous nerve cells are apoptosed.
Trophic factors are required for the nerve cells to live - in their absence, apoptosis is induced
Describe the appearance of apoptosic cells in general
Shrunken cells w/ membrane blebs and then fragment, releasing small membrane bound blebs >>> then taken up by macrophages
Intracellular contents not released (compared to necrotic cells), prevents inflammation
Describe the pathway when trophic factors are present
When trophic factors are present, BAD is phosphorylated, where cytochrome C is not released and caspase cascade not induced
Describe the process when trophic factors are NOT present
BAD not phosphorylated, Bax channel opens, leading to efflux of cytochrome C >>> caspase cascade
Cells stop dividing after a pre-set number of divisions and take on a differentiated phenotype (RBC, neuron)
Cells in culture stop dividing after about 50-100 divisions (due to absence of telomerase in adult cells)
When telomeres get too short > p53 activated > p21 cdk inhibitor (blocks cells in G1 > senescence
What are the external influences that affect growth?
1. Growth factors - diffusible signaling molecules, can act locally or systemically (ex. erythropoietin)
2. Cell-ECM interactions - normal cells fail to divide if they're deprived of interaction w/ insoluble matrix (anchorage-dependent cell growth)
3. Cell-cell interactions - normal cells exhibit density dependent growth inhibition (contact inhibition)
How are different tissues (nerve/cardiac muscle/liver/skin) maintained?
Nerve and cardiac muscle cells are permanent cells - survive as long as the organism
Liver replications by simple duplication
Skin regenerates from undifferentiated stem cells (basal lamina)
Describe the signaling cascades of growth
Growth control is a balance of stimulatory and inhibitory signals (ex. kinases and phosphatases)
How do cancer cells differ from "normal" cells?
Cancer cells may have some of these characteristics:
They do not senesce
Lack growth factor dependence
Lack anchorage dependence
No cell-cell contact inhibition
Most cancers stem from mutaiton of oncogenes and tumor suppressor genes
Disregulated (mutated or overexpressed) versions of genes normally found in cells (these are called proto-oncogenes)
Conversion from proto-oncogene to oncogene usually result of somatic mutaiton
Give some characteristics of proto-oncogenes
Proteins that normally stimulate growth
Conversion to oncogene results in elevated and/or unregulated activity
Mutation of SINGLE allele of proto-oncogene can cause abnormal growth
Tumor suppressor genes
Genes normally found in cellular genomes
Normally function to oppose activity of proto-oncogenes (normally inhibit growth)
Cells lose growth control when these are mutated to inactive form
Both alleles must be mutated or deleted (loss of heterozygocity)
First mutation/deletion is often inherited (individuals are predisposed to developing cancer)
(Ex. Inactive Rb protein leads to retinablastoma, mutated p53)
Describe actions of viral proteins on Rb and p53
DNA viruses carry genes that encode proteins that block Rb and p53
Leads to hyper proliferation of cells
Occurs in HPV
What are the stages in cancer progression?
Loss of cell divisions/growth control > Tumor (neoplasm) > Ability to invade/metastasize > Malignant tumor > Cancer
The development of cancer takes at least how many mutations?
7 - tumor suppressors (2 mutations each), proto-oncogenes (1 mutation)