caa a22 4500 606236732 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2342-1 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2342-1 Mitogen-activated protein kinase signaling controls basal and oncostatin M-mediated JUNB gene expression [Elektronische Daten] [Mellissa Hicks, Qiuping Hu, Erin Macrae, James DeWille] The mitogen-activated protein kinase (MAPK) pathway is aberrantly activated in many human cancers, including breast cancer. Activation of MAPK signaling is associated with the increased expression of a wide range of genes that promote cell survival, proliferation, and migration. This report investigated the influence of MAPK signaling on the regulation and expression of JUNB in human breast cancer cell lines. JUNB has been associated with tumor suppressor and oncogenic functions, with most reports describing JUNB as an oncogene in breast cancer. Our results indicated that JUNB expression is elevated in MCF10Amet, SKBR3, and MDA-MB-231 human breast cancer cell lines compared to nontransformed MCF10A mammary epithelial cells. Increased RAS/MAPK signaling in MCF10Amet cells correlates with the increased association of RNA polymerase II (Pol II) phosphorylated on serine 5 (Pol IIser5p) with the JUNB proximal promoter. Pol IIser5p is the "transcription initiating” form of Pol II. Treatment with U0126, a MAPK pathway inhibitor, reduces Pol IIser5p association with the JUNB proximal promoter and reduces JUNB expression. Oncostatin M (OSM) enhances MAPK and STAT3 signaling and significantly induces JUNB expression. U0126 treatment reduces OSM-induced Pol IIser5p binding to the JUNB proximal promoter and JUNB expression, but does not reduce pSTAT3 levels or the association of pSTAT3 with the JUNB proximal promoter. These results demonstrate that the MAPK pathway plays a primary role in the control of JUNB gene expression by promoting the association of Pol IIser5p with the JUNB proximal promoter. Springer Science+Business Media New York, 2015 Mitogen-activated protein kinase (MAPK) nationallicence Oncostatin M (OSM) nationallicence JUNB nationallicence RNA polymerase II nationallicence Breast cancer nationallicence Hicks Mellissa Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut Hu Qiuping Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut Macrae Erin Division of Solid Tumor Oncology, Department of Internal Medicine, College of Medicine, Ohio State University, 43210, Columbus, OH, USA aut DeWille James Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 115-124 0300-8177 403:1-2<115 2015 403 11010 https://doi.org/10.1007/s11010-015-2342-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2342-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hicks Mellissa Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Hu Qiuping Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Macrae Erin Division of Solid Tumor Oncology, Department of Internal Medicine, College of Medicine, Ohio State University, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- DeWille James Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, 43210, Columbus, OH, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 115-124 0300-8177 403:1-2<115 2015 403 11010