The organized structure of normal breast epithelial cells may also serve as a barrier against cancer, according to a study by University of Helsinki scientists. The work appears this week in the online edition of the Proceedings of the National Academy of Sciences (PNAS).
Finnish researchers found that the tightly organized architecture of mammary epithelial cells is a powerful restraint against the cancer gene provoked inappropriate proliferation. Their study also links function of a tumor suppressor gene to the development of cancer gene resistant epithelial organization.
"Rogue cancer genes can force epithelial cells to proliferate and proliferation of malignant cells will certainly disrupt the organized epithelial structure. However, there has always been this chicken or the egg problem: Does cancer gene initiate cell proliferation, which causes disruption of the epithelial structure or does loss of tissue structure come first, creating suitable environment for cancer genes to enforce the cell cycle progression?" explains the research team leader Juha Klefstrom, Ph.D. The present study supports the idea that loss of tissue structure comes first.
Experiments with fly models have shown that loss of epithelial organization can enhance the tumorigenic potential of cancer genes (oncogenes) and these findings prompted Juha Klefstrom's team to explore whether the formation of epithelial organization works other way around and suppresses oncogene function. "We were amazed to find out that the formation of organized mammary epithelial architecture in three-dimensional organotypic cell culture correlated with complete loss of oncogenic activities of c-Myc cancer gene" says Klefstrom.
Johanna Partanen, a graduate student in Klefstrom's laboratory and lead author in the article, continues "We also asked how to dismantle the proliferation resistance of the epithelial organization. To find clues to genes involved in the development of organized epithelial structure, we turned back to fly". Epithelial cells of both flies and humans live their lives in the companionship of others, held together by tight belt of adhesion proteins and interactions with supporting extracellular matrix. Developmental geneticists working with fly models have identified an important group of genes, PAR genes, which regulate the development of highly ordered epithelial cell organization. "Most interesting candidate for us was LKB1, the human homologue of Par4 protein, because this gene has strong connection to human epithelial disorders" says Partanen. Previous research done by Akseli Hemminki, Lauri Aaltonen and Tomi Mäkelä at the University of Helsinki has linked this gene to Peutz-Jeghers cancer predisposition syndrome and it has also been suggested that LKB1 has tumor suppressor functions in several epithelial cancers. Klefstrom's team found that epithelial cells missing the LKB1 protein are able to form only cancer-like disorganized epithelial structures. This disorganized environment enables c-Myc oncogene to drive inappropriate cell proliferation.
The study demonstrates that organized epithelial structure can suppress malignant actions of cancer genes and identifies LKB1 tumor suppressor gene as an architect of this proliferation resistant organizational plan. The ordered structure of epithelial cells is frequently lost in epithelial tumors, like breast carcinoma, and the study suggests that loss of structure may play more active role in progression of tumors than previously anticipated.
This study was funded by the Academy of Finland, Finnish Funding Agency for Technology and Innovation (TEKES), the Sigrid Juselius Foundation, Helsinki University Central Hospital, the Lilly Foundation, and the Juliana von Wendt Foundation.
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy