Navigation Links
New Path from Estrogen to Survival in Breast Cancer Cells Described

After years of research, scientists at The University of Texas M. D. Anderson Cancer Center are now able to explain, in exquisite// molecular detail, how the estrogen hormone can help keep breast cancer cells alive.

In the Sept. 24 issue of the journal, Nature Cell Biology, they assign roles to a number of genes and proteins thought to play a part in breast cancer cell survival, and in the process, have identified potential molecular drug targets.

"It's a very complex story, but we have been able to bring together a number of basic discoveries from different fields of research to work out the basic mechanism by which estrogen can exert a pro-life effect on cancer cells," said the study's lead author, Edward T. H. Yeh, M.D., professor and chair of The University of Texas M. D. Anderson's Department of Cardiology.

Along the way, the researchers have provided some novel insights. One is that they have provided a role for breast cancer-associated protein 3 (BCA3), which had been recently found to be over-expressed in both breast and prostate cancers. Yeh and his team show that this protein, by itself, doesn't have any relationship to the cancer, but when modified by the protein NEDD8, can act like a tumor suppressor.

The researchers also found that SIRT1, a key protein involved in this molecular pathway, is a member of a family of proteins responsible for prolonging life span in both yeast and worms. "The fact that these molecules, which maintain life span in other species, has been found to be involved in suppressing cancer development seems important to us," Yeh said. "The reason people live longer is that they don't develop cancer as readily."

Players in this newly defined pathway are:

* BCA3, which had no known function. * NEDD8, a protein that can bind to other proteins and alter their function. * SENP8, a protease (enzyme) that can break bonds between other molecules. * SIRT1 * NFkB (Nucle ar Factor kappa B), a family of proteins that turn on genes involved in cell death (apoptosis) and cell proliferation. When over-expressed, NFkB can protect cells from undergoing apoptosis, and in general, the more NFkB is expressed, the more resistant the cell is to apoptosis. * Estrogen, a hormone that acts as growth fuel for about 70 percent of breast cancers.

Researchers are interested in ways that cells can efficiently turn genes on or off, and one of the newest mechanisms is dubbed "NEDDylation," which Yeh helped to find 10 years ago. This process requires multiple enzymes to attach NEDD8 to other proteins.

To find proteins that can be altered by NEDD8, the four-member research team used yeast as their experimental platform, and SENP8 as a tool. This enzyme is known to be able to separate NEDD8 from the proteins it binds to. In this way, they could use SNEP8 "as bait" to fish for protein complexes held together by NEDD8.

They first found that BCA3 binds to SENP8 and was modified byNEDD8, and then discovered that this complex affects NFkB signaling. It does this by binding on to p65, one of the two proteins that make up NFkB proteins, the researchers say. "NEDD8 modified BCA3 regulates the activity of NFkB, but BCA3 alone does not have any impact on NFkB," says Yeh.

Then they looked at how this NEDDylation further works to suppress the ability of NFkB to transcribe (activate) other genes. Here the investigators found SITR1, the molecule known to prolong life span in several other species. SITR1 is a histone deacetylase, a protein that blocks transcription factors from regulating genes. "When NEDD8 modified BCA3, it binds to p65 and recruits SITR1 to suppress NFkB-mediated transcription," Yeh said.

Finally, the researchers discovered that estrogen blocks NEDD8 from modifying BCA3, a finding which goes some way to "explaining estrogen's pro-life effect in breast cancer cells," Yeh says. "Estrogen could enhance the survival of breast cancer cells by silencing BCA3, through eliminating its hold on NFkB transcription."

Now that this cancer-promoting molecular pathway has been described, Yeh says it might be possible to interfere with a number of the players to inhibit cancer growth. "NEDD8 is key," he said. "It may be possible to design drugs that block the removal of NEDD8 from BCA3." By increasing the amount of NEDD8-modified BCA3, there will be a corresponding decrease in the level of NFkB and the cancer cells will be more sensitive to chemotherapy, Yeh says.

"There is a lot we need to sort out, of course, but this is a model of how estrogen may function to promote growth in breast cancer that we can all now work from," Yeh says.

Source-Newswise
'"/>




Related medicine news :

1. Estrogen lowers cancer risk
2. Estrogen Does Not Prevent Recurrent Strokes
3. Herbs With Estrogen Action Aggravate Cancer Risk
4. Osteoarthritis and Estrogen are connected
5. Estrogen Patch is Safer than Pills for Heart
6. Estrogen in Food Reduces Cancer Risk
7. Estrogen Found To Protect the Colon Against Cancer
8. The Side Effects Of Estrogen Therapy
9. The Effects Of Estrogen Therapy
10. A Likely Use For Estrogen Therapy
11. Preventing Colon Cancer With Estrogen
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:10/12/2017)... ... October 12, 2017 , ... ... for healthcare compliance program management, will showcase a range of technology and learning ... Assisted Living (NCAL) Convention and Expo to be held October 14–18, 2017 at ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... meet the demand of today’s consumer and regulatory authorities worldwide. From Children’s to ... and tested to meet the highest standard. , These products are also: ...
(Date:10/12/2017)... ... , ... Asante, a nationally recognized health system in southern ... home health joint venture through an agreement, effective October 1, 2017, to create ... health company with Asante, delivering clinically integrated care, for the past eight years. ...
(Date:10/12/2017)... ... October 12, 2017 , ... HMP , a leader ... a 2017 Folio Magazine Eddie Digital Award for ‘Best B-to-B Healthcare Website.’ Winners were ... 11, 2017. , The annual award competition recognizes editorial and design excellence across a ...
(Date:10/12/2017)... ... October 12, 2017 , ... Women-owned and Grand ... Best and Brightest in Wellness® by Best and Brightest. OnSite Wellness will be ... Oct. 20 from 7:30 a.m. to 2 p.m. at the Henry Autograph Collection ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... Sept. 22, 2017 AVACEN Medical (AVACEN) announced ... now successfully helping those with the widespread pain associated ... diagnosed Amanda in Essex, England ... my hair, experiencing no sleep at all, tremendous pain, ... I cannot recommend [the AVACEN 100] enough, how this ...
(Date:9/19/2017)... Ky. , Sept. 19, 2017   ZirMed Inc ... predictive analytics, today announced that it has been ranked #1 ... Black Book™ Rankings 2017 User Survey. ZirMed was ... solution for large hospitals and medical centers over 200 beds ... Black Book,s healthcare technology user survey history. ...
(Date:9/18/2017)... , Sept. 18, 2017 ... fields of bioinformatics and immune engineering, today ... protective avian influenza A (H7N9) vaccine. ... related to seasonal influenza and presents a ... on prior exposure to be effective. Using ...
Breaking Medicine Technology: