Turning off cancer using anti-sense oligonucleotides

[S.A.M.]

The Eukaryotic Tranaslation Initiation Factor 4 E is an important component of the signaling cascade that leads to the initiation of translation. As you can see in the picture below, translation initiation is part of the cascade of PI3K or phosphoinositide 3 kinase, a potent stimulator of cell growth. It is believed to be a proto-oncogene and is elevated in several cancers. It also blocks apoptosis or cell death through downstream regulation of Protein kinase B or PKB.

Elevated PI3K or mTOR can lead to increased expression (and hence activity) of EIF4E, which in turn can lead to increase in tumor size. Control of EIF4E expression is therefore an attractive option in anti-cancer therapy.

Link to figure:
http://www.massgeneral.org/neurology/Reeves/Research Images/mtoract.jpg

In a recent study, the authors used EIF4E specific anti-sense oligonucteotides, which bind to the target EIF4E RNA and mediate its destruction to regulate the amount of EIF4E present.

This had the effect of reducing translation initiation and hence cell growth, reducing the tumors in mice with no apparent side effects.

More.

 

[Exhumed]

I'm surprised that there were no side-effects if EIF4E was reduced everywhere. The way I read it at first was that EIF4E was used in part of signal cascades for all/a large amount of translation. Though it makes intuitive sense that the cancer cells would be more sensitive.

 

[S.A.M.]

If there are effects in cell growth or proliferation, I would assume they would show up over time. As it is the EIF4E is just one of several translation initiation factors.


More on EIF4E

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=135594

 

[Atom]

Where can I buy them?

<< lights up another oily rag >>

 

[Exhumed]

Ah, thanks for explaining that.

 

[S.A.M.]

Not sure if I was clear, but its my assumption that at the point where you've developed the tumor, you're not really concerned with your potential growth; its a question of trade-offs even in children with tumors.

 

[Exhumed]

Sounds good

 

[TruthSeeker]

So does the EIF4E only affect cancerous cells?

 

[S.A.M.]

From previous link :bugeye:

Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting component of translation initiation, and its activity is tightly regulated in cells (13, 35). Regulation of eIF4E activity is critical to normal cell growth, as overexpression of eIF4E in rodent cells is oncogenic (22), while injection of eIF4E into quiescent NIH 3T3 cells induces DNA synthesis (38)

 

[TruthSeeker]

Oh, ok... so it only limits the growth of cells... alright....