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:6/20/2017)...  Hill-Rom Holdings, Inc. (NYSE: HRC), will host its fiscal ... July 28, 2017, beginning at 7:30 a.m. (CDT) / 8:30 ... To participate in the conference call, dial (877) 304-8969 (domestic) ... least 10 minutes prior to the start to allow time ... Webcast: A simultaneous webcast of the ...
(Date:6/16/2017)... , June 16, 2017  Exactly 50 years ago ... off what later became known as the San Francisco "Summer ... ) is unveiling two radical innovations in strategic market research ... This announcement marks the beginning of Northern Light,s "Summer of ... ...
(Date:6/14/2017)... -- In 2016, Embodied Labs took top prize ... came away with $25,000 in seed-fund investment. Embodied Labs ... "entering the life of another" and by the Journal ... medical professionals in an entirely new dimension." Building upon ... for the Department of Education,s EdSimChallenge, where they received ...
Breaking Medicine Technology:
(Date:6/24/2017)... ... 24, 2017 , ... The weather is heating up and the days are ... should be aware that the summer months provide more than warmer temperatures that are ... can be negatively affected from direct exposure to the sun. When it comes to ...
(Date:6/23/2017)... , ... June 23, 2017 , ... By scoring 100% ... ninth consecutive four-star rating from premier online charity evaluator, Charity Navigator, validating ANRF's work ... 1% of all charities reviewed by Charity Navigator and earns ANRF a spot on ...
(Date:6/23/2017)... (PRWEB) , ... June 23, 2017 , ... ... plastic surgeon practicing in Newburgh, New York, has recently begun offering three new ... to offering the best cutting-edge procedures and reducing downtime, Dr. Rubinstein is excited ...
(Date:6/23/2017)... Hills, CA (PRWEB) , ... June 23, 2017 , ... ... plane facelift . Dr. Talei has come up with a proprietary technique that ... releases and lifts tissues that have dropped. For all ages, patients can expect to ...
(Date:6/23/2017)... (PRWEB) , ... June 23, 2017 , ... MD ... Florida. This is MD Now’s 28th facility overall and marks the urgent care center's ... located one mile North of The Falls shopping mall. The new clinic offers a ...
Breaking Medicine News(10 mins):