Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular master switch for pancreatic cancer identified, potential predictor of treatment outcome

13.02.2013
A recently described master regulator protein may explain the development of aberrant cell growth in the pancreas spurred by inflammation

A team from the Perelman School of Medicine at the University of Pennsylvania profiled gene expression of mouse pancreatic ductal and duct-like cells from different states - embryonic development, acute pancreatitis and K-ras mutation-driven carcinogenesis - to find the molecular regulation of these processes.


An intermediate cell type which emerges during inflammation and regeneration in acute pancreatitis regulated by the transcription factor Prrx1, termed acinar-to-ductal metaplasia.

Credit: Maximilian Reichert, MD, Perelman School of Medicine, University of Pennsylvania

Broadly speaking, two cellular compartments are important in a normal pancreas, endocrine cells, which produce hormones including insulin, and exocrine cells – acinar and ductal -- which make and secrete digestive enzymes.

A cover article from the lab of Anil Rustgi, MD, Chief, Division of Gastroenterology, published early online in Genes and Development, details the molecular changes of exocrine cells during inflammation, so-called acinar-ductal metaplasia (ADM), a prelude to pancreatic ductal adenocarcinoma.

They used cell lineage tracing to follow what happens to the regulator protein called Prrx1 as cells change characteristics. Another protein, Sox9, which is downstream of Prrx1 in the cell signal pathway, is also important in understanding how pancreatic cancer forms, as the group has established the first link of Prrx1 to Sox9. The findings suggest that Prrx1 and Sox9 influence the emergence of an intermediate cell type that can give rise to cancer.

Inflammation is Key Culprit

Inflammation of the pancreas, or pancreatitis, is a leading reason for hospital admission, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and chronic pancreatitis is a risk factor for cancer of the pancreas. Each year, about 210,000 people in the United States are admitted to the hospital with acute pancreatitis.

Acute pancreatitis is caused by alcohol abuse, gallstones, and autoimmune disorders. When things go wrong, inflammatory pancreatitis happens, and the change from an acute state to a chronic state can lead to cancer.

When a patient recovers from pancreatitis, the change in cell fate reverts to the original cell type. But, if the pancreatitis is chronic, changed cells stay changed.

"We hope that studies like this one that identify key molecules and pathways that govern the cancerous fate of cells can be used as diagnostic predictors of treatment outcome and severity for cancer," says Rustgi.

Co-authors include first author Maximilian Reichert, Shigetsugu Takano, Johannes von Burstin, Kaori Ihida-Stansbury, Christopher Hahn, Steffen Heeg, Andrew D. Rhim, and Ben Z. Stanger, all from Penn

The work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK060694, P30-DK050306, DK088945, DK007066, CA117969, DK083355, DK083111), the National Pancreas Foundation , the Honjo International Scholarship Foundation , the Deutsche Krebshilfe, the American Society Grant (RP-10-033-01-CCE).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>