Navigation Links
Inverted DNA turns quiet developmental gene into a potent driver of t-cell lymphoma
Date:2/27/2008

A gene crucial for embryonic development can quickly become a potent cancer promoter in adult mice after a genetic misalignment, according to researchers from Fox Chase Cancer Center, causing white blood cells to become cancerous spontaneously.

In the March 1 issue of the journal Cancer Research, the researchers detail how a gene called Dlx5 works cooperatively with a known oncogene, Akt2, to drive cancer in mice. The protein that Dlx5 encodes could be a target for drugs to slow the growth of lymphomas and other cancers in humans, they say.

A chromosomal inversion essentially flips a segment of DNA, placing the Dlx5 gene next to an enhancer in a neighboring gene, which in turn activates a number of other nearby genes, says lead investigator Joseph Testa, Ph.D., a cancer geneticist at Fox Chase. The result is like placing a V8 engine on a Flexible Flyer something is going to go fast and without much control.

According to Testa, Dlx5 is basically a good gene that starts to do bad things when it moves into a dangerous neighborhood. Dxl5 is part of the homeobox family of genes, which direct the timing of events in the physical development of a growing fetus, such as when to sprout a limb, for example. In adults, such genes are almost entirely inactive.

Unfortunately, in white blood cells, such as T cells, Dlx5 moves to a region of DNA involved in the genetic rearrangement that allows immune cells to switch genes around in order to create new combinations of proteins to respond to disease threats. This recombination process allows B cells to generate antibodies and T cells to generate T cell receptors, enabling the immune system to recognize an enormous array of foreign bacteria, viruses and parasites.

In a mouse model of T cell lymphoma, the researchers found that mice bred to over-express the Akt2 gene also over-expressed Dlx5. In fact, the researchers found the chromosomal inversion that led to cancer was a feature in the majority of mice studied. One particular line of transgenic mice exhibited the inversion in 15 of 15 tumors they examined. Genetic recombination is a frequent component of T-cell malignancies, but it is startling to see this same pattern come up repeatedly, Testa says.

In subsequent cell studies, Testa and his colleagues determined that the combined activation of both Dlx5 and Akt2 could result in increased cell growth and proliferation. While their findings are the first to assert that Dlx5 can be an oncogene, the gene has previously been implicated in a number of human endometrial and lung cancers. Moreover, the DLX5 protein was found in abundant amounts within three out of seven human lymphomas that the Fox Chase researchers examined.

According to Testa, molecules that could bind and inhibit DLX5 could provide a more useful drug for therapeutic development than could molecules that inactivate AKT2.

The AKT family of proteins is crucial to survival in both cancerous and non-cancerous cells, so AKT2 is a potentially risky target for drug development since blocking AKT2 can also kill healthy cells, Testa says. DLX5, however, is not generally active in healthy adult cells, so it represents a much more druggable target for inhibition.


'/>"/>

Contact: Greg Lester
gregory.lester@fccc.edu
215-728-2753
Fox Chase Cancer Center
Source:Eurekalert

Related medicine news :

1. ORBIS Internationals Flying Eye Hospital Returns to Myanmar
2. Study Shows New Therapy Opens Blocked Fallopian Tubes, Returns Fertility Without Surgery
3. The Search for Healthier Drinks Turns Up Yerba Mate
4. Gilbert Hospital Turns the Tables on the Flu
5. Small Business Turns Out on Super Tuesday
6. Gilbert Hospital Turns Two
7. San Francisco City Hall Turns Pink, Draws Attention to Disparities in Breast Cancer Screening, Treatment
8. Speaking of Womens Health Community Event Returns to All Wal-Mart Supercenters Nationwide January 12th
9. Brain Turns to Positive Thoughts When Faced With Death
10. Fitness Sensation Susan Powter Returns to Her Legions of Fans and Followers with Focus on Whole Body Wellness Program
11. Childrens Hospital Los Angeles Turns Off the Tap With Green Earth Waterless Carwash
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/24/2017)... ... July 24, 2017 , ... Cosmetic Town, an online plastic surgery ... surgeries they perform on a daily basis. , The new video series will ... specialize in at their practices. , When asked about the new video series, ...
(Date:7/24/2017)... ... July 24, 2017 , ... ... effectively destroyed the construction site and threatened numerous homes and businesses nearby, causing ... article on NBCLosAngeles.com. Los Angeles Area consulting firm Fire Protection Group, Inc. ...
(Date:7/24/2017)... , ... July 24, 2017 , ... Every year, thousands ... and educational conference, InstructureCon. Each annual event is coupled with a dynamic theme like ... a James Bond theme, Mission: InstructureCon 0017. , To extend their partnership with ...
(Date:7/24/2017)... PHILADELPHIA (PRWEB) , ... July 24, 2017 , ... ... Health , two organizations that already work hand-in-hand on an Innovation Collaboration program, ... transform the access, quality, experience and cost of the care members and patients ...
(Date:7/24/2017)... ... July 24, 2017 , ... Anyone who uses scales know they have ... a pharmacist using that same scale to dispense medication. The first example is an ... illustrations show why it is important to have the right balance for the process. ...
Breaking Medicine News(10 mins):
(Date:7/19/2017)... N.C. , July 19, 2017  Mako Medical ... Affairs, and the Military Family Assistance Fund (MFA) to ... to visit with their families one last ... funding to coordinate the travel and logistics needed for ... our deployed soldiers and their families. We just wish ...
(Date:7/13/2017)... Medical Products, a leader in medical product innovation and global patient ... for hospice patient care. ... Centurion Medical Products ... pain management and emotional comfort are part of a hospice,s primary ... preventing unneeded emergency department admission due to severe fecal impaction. One ...
(Date:7/11/2017)... 11, 2017 Zymo Research Corp., also known as ,The Epigenetics ... biological aging in a precise manner using the myDNAge ™ test. ... a professor of human genetics and biostatistics at the David Geffen ... Health , Zymo Research,s proprietary DNAge ™ technology is used to ... ...
Breaking Medicine Technology: