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.
‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie
Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Earth Sciences
24.10.2016 | Life Sciences
24.10.2016 | Physics and Astronomy