Lecture 29 - Cellular Development and Cancer.doc

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21 Mar 2012
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Lecture 29
Growth Factors
Growth Factors inhibit cellular apoptosis and are known as survival factors
oSurvival factors usually bind to membrane receptors which activates
signaling pathways that prevents apoptosis
By supressing apoptosis activating pathways
By activating apoptosis supressing pathways
Mitogens are also survival factors that propel the cell into mitosis
Nerve cells compete for the survival factors secreted by their target cells. This
ensures that only a necessary level of cells exist, excess cells die.
The more growth factor the nerve cell receives, the larger it grows. Compared
to a neutrophil cell, it is much larger.
The mTOR pathway (Mammalian Target of Rapamycin)
1. Growth factors bind to cell membrane receptors which dimerize and become
phosphorylated
2. The phosphorylated growth factor receptor activates a PI 3 kinase
(phosphoinositide 3 kinase)
3. The PI 3-kinase phosphorylates a an inositol phospholipid at the 3 position
4. Activated inositol phospholipids may activate a TOR kinase (a kinase targeted
by Rapamycin drug therapy to treat cancer – by inhibiting growth).
5. The TOR kinase can activate a S6 kinase or inhibit a 4e-BP (binding protein)
a. S6 (a ribosomal protein) is activated by S6-k phosphorylation to increase
translation of a subset of mRNA increasing protein production
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b. 4e-BP binds to eIF4E (translation initiation factor; brings in ribosomes to
5’ end of mRNA), inhibiting eIF4E from binding to mRNA.
Phosphorylating 4e-BP inactivates it, releasing eIF4E, now free to bind to
mRNA to increase translation.
Cell Cycle and Nutrition – the effects of Mutations
With adequate nutrition, cells are able to grow, duplicating its cell mass
(organelles)
When the peak mass is achieved, the cells proceeds through division
oHowever, if there is an inadequate amount of nutrition, cells will prolong
their growth phases until the correct amount of cellular mass is achieved
oThis ensures that daughter cells have the adequate components of a
normal cell
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