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Archive - Sep 11, 2017


DNA Looping Architecture May Lead to Opportunities to Treat Brain Tumors

The discovery of a mechanism by which normal brain cells regulate the expression of the NFIA gene, which is important for both normal brain development and brain tumor growth, might one day help improve therapies to treat brain tumors. The study was published online on September 11, 2017 in Nature Neuroscience. This article is titled “Glia-Specific Enhancers and Chromatin Structure Regulate NFIA Expression and Glioma Tumorigenesis.” "We began this project by studying how three components that regulate the expression of the NFIA gene interact with each other in the developing spinal cord in animal models," said corresponding author Dr. Benjamin Deneen, Associate Professor of Neuroscience at the Center for Stem Cell and Regenerative Medicine and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. The researchers studied primarily glial cells (image), which represent 70 percent of the cells in the central nervous system and support the functions of the neurons. Gene expression, the process by which genes produce proteins, is regulated at different levels, in a coordinated fashion, but scientists don't completely understand how these levels interact. Dr. Deneen and his colleagues explored how three levels of gene regulation coordinated their activities to regulate NFIA gene expression. The researchers studied enhancers, (sections of DNA that are located at a distance from the NFIA gene and can influence gene expression), transcription factors (proteins that bind to enhancers), and the three-dimensional architecture of the associated DNA. First, the scientists identified enhancers involved in the regulation of expression of NFIA gene using a non-traditional approach.

Epigenetic Changes from Cigarette Smoke May Be First Step in Lung Cancer Development

Scientists at the Johns Hopkins Kimmel Cancer Center say they have preliminary evidence in laboratory-grown, human airway cells that a condensed form of cigarette smoke triggers so-called "epigenetic" changes in the cells consistent with the earliest steps toward lung cancer development. Epigenetic processes are essentially switches that control a gene's potentially heritable levels of protein production but without involving changes to underlying structure of a gene's DNA. One example of such an epigenetic change is methylation -- when cells add tiny methyl chemical groups to a beginning region of a gene's DNA sequence, often silencing the gene's activation. "Our study suggests that epigenetic changes to cells treated with cigarette smoke sensitize airway cells to genetic mutations known to cause lung cancers," says Stephen Baylin, MD, the Virginia and D.K. Ludwig Professor for Cancer Research and Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. Details of the scientists' experiments are described in the September 11, 2017 issue of Cancer Cell. The article is titled “Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations.” For two decades, scientists have known some of the genetic culprits that drive lung cancer growth, including mutations in a gene called KRAS, which are present in one-third of patients with smoking-related lung cancers, according to Dr. Baylin. Genetic and epigenetic changes also occur when normal cells undergo chronic stress, such as the repeated irritation and inflammation caused by decades of exposure to cigarette smoke and its contents. Dr.

Internal Mechanism Found Responsible for Limitless Growth Potential of Epithelial Tumors

Researchers from the Development and Growth Control Laboratory at IRB Barcelona have identified the cell types and molecular mechanism responsible for the unlimited growth potential of epithelial tumors (carcinomas) and demonstrated that the growth of these tumors is independent of the tumor’s microenvironment. "In epithelial tumors caused by chromosomal instability or loss of cell polarity, the interaction between two tumor cell populations drives malignant growth," explains Dr. Marco Milán, ICREA Research Professor and Head of the laboratory. Published as the cover story of the August 29, 2017 issue of PNAS, the study analyzes solid tumors of epithelial origin in the fruit fly Drosophila melanogaster. "We have induced tumor development in two ways--by generating genomic instability and the loss of cell polarity. We have validated the causal relation between these two conditions--which are frequently observed in carcinomas--and the development of tumors," explains Dr. Mariana Muzzopappa, first author of the study and postdoctoral fellow in the Development and Growth Control Lab. The PNAS article is titled “Feedback Amplification Loop Drives Malignant Growth in Epithelial Tissues.” To study the effect of the microenvironment on tumor development, the researchers examined tumor growth in the absence of adjacent cell populations, such as cells of the immune system or mesenchymal cells, which can act as a niche by supplying tumors with growth factors. The scientists observed that the tumor continued to grow in the absence of these two cell types. Furthermore, they demonstrated that "the growth of epithelial tumors is dependent on activation of the JNK stress signaling pathway and that this pathway is intrinsically activated in the tumor, regardless of its microenvironment," highlights Dr. Milán.