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Stem-cell activators switch function, repress mature cells
Ohio State University Medical Center via ^ | December 16, 2009 | NA

Posted on 12/26/2009 10:39:37 AM PST by neverdem

In a developing animal, stem cells proliferate and differentiate to form the organs needed for life. A new study shows how a crucial step in this process happens and how a reversal of that step contributes to cancer.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, shows for the first time that three proteins, called E2f1, E2f2 and E2f3, play a key role in the transition stem cells make to their final, differentiated, state.

These proteins help stimulate stem cells to grow and proliferate. But once stem cells begin to differentiate into their final cell type – a cell in the retina or in the lining of the intestine, for example – the same three proteins switch function and stop them from dividing any more.

The research also shows how these proteins can switch course yet again in cells that have mutations in the retinoblastoma (Rb) gene. Mutated Rb genes occur in many types of cancer, suggesting that these E2f proteins might offer a safe and novel therapeutic target in these tumors.

The findings are published in back-to-back papers in the Dec. 17 issue of the journal Nature.

"We show that these E2fs are gene activators in stem cells but then switch to gene repressors when stem cells begin differentiating," says Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at Ohio State's James Cancer Hospital and Solove Research Institute. Leone headed the first of the two Nature studies and is a co-author on the second.

"This is a very important step in the process of differentiation," Leone says. "As organs form during development, there comes a time when their growth must stop because an organ needs only a certain number of cells and no more. The switch by these proteins from activators to repressors is essential for that to happen. "Before this, there was no suspicion that these regulatory proteins had any role in differentiated cells," says Leone. "It was thought they were important only in proliferating cells like stem cells. But that's not true."

Leone and his colleagues show the function of the proteins in differentiation in mouse embryos, retinas, lenses and intestines.

They also show how the three proteins could revert back to gene activators in cancer cells and promote tumor growth in cancers with Rb mutations. "In this case, these proteins are acting abnormally relative to the surrounding tissue, so they might provide a safe therapeutic target," Leone explains. "If we can inactivate these E2fs in cancer cells, perhaps we can prevent further tumor growth without having a major affect on healthy cells."

Source : Ohio State University Medical Center

TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: cancer; e2f; science; stemcellresearch; stemcells
E2f1–3 switch from activators in progenitor cells to repressors in differentiating cells

Division and apoptosis of E2f-deficient retinal progenitors

However, loss of activating E2fs caused downregulation of the p53 deacetylase Sirt1, p53 hyperacetylation and elevated apoptosis, establishing a novel E2f–Sirt1–p53 survival axis in vivo. Thus, activating E2fs are not universally required for normal mammalian cell division, but have an unexpected pro-survival role in development.

1 posted on 12/26/2009 10:39:40 AM PST by neverdem
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To: Coleus; Peach; airborne; Asphalt; Dr. Scarpetta; I'm ALL Right!; StAnDeliver; ovrtaxt; ...

Merry Christmas stem cell ping!

2 posted on 12/26/2009 10:42:06 AM PST by neverdem (Xin loi minh oi)
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To: neverdem
and Richard J. Solove Research Institute

Yikes, I misread that as "James G. Sokolove" (famous trial lawyer).


3 posted on 12/26/2009 10:43:24 AM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: neverdem

Thanks. Nice article...

4 posted on 12/26/2009 10:51:41 AM PST by DoughtyOne (Good news. HC bill will not cover illegal aliens. Bad news. 20-35 million will become citizens.)
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To: DoughtyOne

I read these stories just to see if I can pronounce the words.

5 posted on 12/26/2009 11:00:27 AM PST by Vermont Lt (I have lived here all my life, and now is the first time I am ashamed of my country)
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To: Vermont Lt

LOL, I hear ya. I can get through most of it, but I know what you mean.

6 posted on 12/26/2009 11:13:38 AM PST by DoughtyOne (Good news. HC bill will not cover illegal aliens. Bad news. 20-35 million will become citizens.)
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To: neverdem

Are these proteins in cheese?

Okay, I guess that just the right ones would have to be routed to the tumor.

7 posted on 12/26/2009 11:22:50 AM PST by decimon
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To: decimon

I’ve been saying for years that what cancer does is turn regular cells back into “early” cells (which grow quickly and follow a code which gives them instructions as to what they are supposed to become — ie., an organ). Except that, somehow the cancer destroys the “code”, so that what grows is just an ambiguous mass of tissue with no function, and which can’t stop growing (since there is no “shut off” code).

This could be a great boon—find the right keys, and we could use turn regular cells back into “early” cells and program them to regrow whatever organs we needed (no more transplants).

8 posted on 12/26/2009 11:33:39 AM PST by CondorFlight (I)
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To: AdmSmith; Berosus; bigheadfred; Convert from ECUSA; dervish; Ernest_at_the_Beach; Fred Nerks; ...
Thanks decimon and neverdem.
9 posted on 12/26/2009 8:53:46 PM PST by SunkenCiv (My Sunday Feeling is that Nothing is easy. Goes for the rest of the week too.)
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