Navigation Links
Protein Found to Shield Pancreatic Cancer Cells from,Self-Destruction

HOUSTON, March 20, 2007 - An overexpressed protein protects human pancreatic cancer cells from being forced to devour themselves, removing one of the body's natural defenses against out-of-control cell growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the March issue of Molecular Cancer Research.

The protein tissue transglutaminase, known by the abbreviation TG2, previously has been found by researchers at M. D. Anderson and elsewhere to be overexpressed in a variety of drug-resistant cancer cells and in cancer that has spread from its original organ (metastasized).

"In general, you rarely see overexpression of TG2 in a normal cell," says Kapil Mehta, Ph.D., professor in the M. D. Anderson Department of Experimental Therapeutics, who began 10 years ago studying TG2 as an inflammatory protein.

Mehta and colleagues in the past year have connected TG2 overexpression to drug-resistant and metastatic breast cancer, pancreatic cancer and melanoma.

Expression of TG2 is tightly regulated in a healthy cell, Mehta says, and is temporarily increased in response to certain hormones or stress factors. "However, constitutive expression of this protein in a cancer cell helps confer protection from stress-induced cell death," Mehta says. "We are developing TG2 as a pharmaceutical target and are now working with a mouse model to that end."

The mechanisms by which TG2 might promote drug-resistance and metastasis have remained elusive, the researchers note. In this paper, the M. D. Anderson team shows in lab experiments that inhibiting the protein in pancreatic cancer cells leads to a form of programmed cell suicide called autophagy, or self-digestion.

TG2 was inhibited in two separate ways. First, the researchers blocked another protein known to activate TG2. Secondly, they also directly targeted TG2 with a tiny molecule known as small interfering RNA tailored to shut down expression of the protein.

In both cases, the result was a drastic reduction of TG2 expression (up to 94 percent) and telltale signs of autophagy in the cancer cells, which became riddled with cavities called vacuoles.

When autophagy occurs, a double membrane forms around a cell organ, or organelle. This autophagosome then merges with a digestive organelle called a lysosome and everything inside is consumed, leaving the vacuole and a residue of digested material. If enough of this happens, the cell dies.

Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics and study co-author, notes that the research also shows that the self-consuming cell death prevented by TG2 is independent of a prominent molecular pathway also known to regulate autophagy called the mammalian target of rapamycin.

"Targeting TG2, or its activating protein PKC, or both, presents a novel and potentially effective approach to treating patients with pancreatic cancer," Lopez-Berestein said. Research in the mouse model remains in the early stages, the researchers caution.

The researchers also show that the TG2 pathway also is separate from another, better known, form of programmed cell death called apoptosis.

Apoptosis, like autophagy, is a normal biological defense mechanism that systematically destroys defective cells by forcing them to kill themselves. In apoptosis, the cells die via damage to their nucleus and DNA, with other cellular organelles preserved. Autophagy kills by degrading those other organelles while sparing the nucleus.

Mehta's lab reported in a Cancer Research paper last September that TG2 overexpression also activates a protein called nuclear factor-kB known to play a role in regulating cell growth, metastasis and apoptosis. This pathway, Mehta explained, could make TG2 an attractive target for other forms of cancer as well.

Co-authors with Mehta and Lopez-Berestein are: co-first authors Ugur Akar, Ph.D., and Bulent Ozpolat, M.D., Ph.D., and Jansina Fok, all of the Department of Experimental Therapeutics, and Yasuko Kondo, M.D., Ph.D, of the M. D. Anderson Department of Neurosurgery.

Funding for this research was provided by the National Cancer Institute of the National Institutes of Health.

- 30 -

M. D. Anderson External Communications Office Media Hotline: (713) 792-0655 http://www.mdanderson.org/mediacenter *************************************************
Contact: Scott Merville, 713-792-0661; sdmervil@mdanderson.org


'"/>




Related medicine technology :

1. Near-Patient Testing: The Advantages of C-Reactive Protein in Hematological Testing
2. Halozyme Therapeutics Enhanze Technology Large Protein Molecule Therapeutic Clinical Trial Results Presented at the 34th Annual Meeting of the Controlled Release Society
3. Pieris Progresses Proprietary Asthma Program: Validation of Pulmonary Delivery of Anticalin-Based Protein Product Candidate
4. DiObex Presents Phase 2a Data of DIO-902 Demonstrating Trends of Improved Glycemic Control and Significant Reductions of LDL-Cholesterol and C-Reactive Protein
5. New Research Results Show That Investigational Drug Phenoxodiol Targets Cancer Protein, Causing Cancer Cell Death
6. Data Show SuperGens Multi-Targeted Tyrosine Kinase Inhibitor Suppresses Critical Double-Stranded DNA Repair Protein, Rad51
7. Data Presented at AACR Meeting Shows Peregrines Immunocytokine Fusion Proteins Reduce Growth of B-Cell Lymphoma Tumors by 85% in Preclinical Studies
8. Study in Cell by Magen BioSciences Co-Founder David E. Fisher Identifies New Roles in Skin Cancer Prevention for Key Tumor Suppressor Protein
9. The International Myeloma Foundation Says Data Reported at a Global Medical Meeting in Greece Demonstrates Improved Survival for a Wide Range of Myeloma Patients
10. Lupus Foundation of America Statement on Results for Clinical Study of CellCept Released by Aspreva Pharmaceutical Company
11. The Christopher and Dana Reeve Foundation Expresses Disappointment Over President Bushs Veto of the Stem Cell Research Enhancement Act
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2016)... BOGOTA, Colombia , June 23, 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a ... second affiliate in Latin America . ... ... ... ...
(Date:6/23/2016)... N.J. , June 23, 2016  Guerbet announced ... Premier Inc.,s Supplier Horizon Award . ... year, Guerbet was recognized for its support of Premier ... creation through clinical excellence, and commitment to lower costs. ... to receive this recognition of our outstanding customer service ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... the "Surgical Procedure Volumes: Global Analysis (United States, ... Australia, Canada)" report to their offering. ... an essential tool for healthcare business planners, provides surgical ... looks at surgery trends with an in-depth analysis of ...
Breaking Medicine Technology:
(Date:6/24/2016)... ... , ... A recent article published June 14 on E Online ... on to state that individuals are now more comfortable seeking to undergo not only ... calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians (BHP) ...
(Date:6/24/2016)... ... ... June 19, 2016 is World Sickle Cell Observance Day. In an effort ... holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a pain ... Disease (SCD) is a disorder of the red blood cells, which can cause episodes ...
(Date:6/24/2016)... ... 24, 2016 , ... The Pulmonary Hypertension Association (PHA) learned ... receive two significant new grants to support its work to advance research and ... by recognizing patients, medical professionals and scientists for their work in fighting pulmonary ...
(Date:6/24/2016)... ... 24, 2016 , ... Dr. Amanda Cheng, an orthodontist ... has extensive experience with all areas of orthodontics, including robotic Suresmile technology, ... , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. It can be used ...
(Date:6/24/2016)... ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain ... for a minimum wage raise to $12 an hour by 2020 and then adjusting it ... the lost value of the minimum wage, assure the wage floor does not erode again, ...
Breaking Medicine News(10 mins):