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.
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy