In a new study, researchers from the Sbarro Health Research Organization Center for Biotechnology Research (SHRO), a cancer, cardiovascular and diabetes research center located in the College of Science and Technology at Temple University in Philadelphia, PA, and at the University of Siena in Siena, Italy examined mechanisms that control Rb2/p130 gene expression in lung fibroblasts and characterize the effects of Rb2/p130 deregulation on the proliferative features of lung cancer cells. Most importantly, their findings reveal why the gene is expressed differently in small and nonsmall lung cancer cells.
The study was funded by SHRO and the Human Health Foundation, a nonprofit biomedical research organization in Terni, Italy. It was published in Molecular Cancer Research.
The new findings disclose the mechanism controlling Rb2/p130 gene expression in lung cells, and that involve two relatively new proteins, CCCTC-binding factor (CTCF) and BORIS (CTCF-paralogue).
"Our research shows that CTCF and BORIS directly regulate Rb2/p130 gene expression in lung cells," says Marcella Macaluso, Ph.D., one of the authors of the study. "We observed that in small lung cancer cells Rb2/p130 exhibits low expression levels, while in non- small lung cancer cells it is overexpressed compared to normal lung cells. However, until now, there were insufficient and conflicting data that did not allow us to precisely link the deregulated expression of Rb2/p130 in lung cancer cells with the genetic mutation of this gene. This study finally disclosed the mechanism and the players controlling Rb2/p130 expression, and these findings have the high potential to provide important information for understanding the proliferative and antiproliferative signals triggered by Rb2/p130."
Also, the research shows that Rb2/p130 is engaged in a complex network of interactions with DNA methyltransferases (DNMTs) and other proteins, including CTCF and BORIS, that are involved in the epigenetic control of chromatin organization and transcription. This complex network of proteins seems to regulate cellular senescence – or aging -- that is a potent anti-cancer mechanism.
"Our studies may provide new insights into the molecular pathways that that are active and correlated to Rb2/p130 expression, new biomarkers for an early diagnosis of lung cancer and/or predictive factors to determine the effect on tumor treatments and insights into the development of therapies based upon clinical modulation of Rb2/p130, CTCF and/or BORIS expression," says Dr. Macaluso.
Future studies are planned to study and decisively dissect the multiple functions of Rb2/p130 in non-small and small cell lung cancer.
Sbarro Health Research Organization Center for Biotechnology Research (www.shro.org) funds the Sbarro Institute for Cancer Research and Molecular Medicine, a leading nonprofit research center for cancer, diabetes, and cardiovascular disease. Based in Philadelphia, Pennsylvania on the campus of Temple University and the University of Siena in Italy, our programs train young scientists from around the globe.
Ilene Raymond Rush | EurekAlert!
Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel
Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences