title: Mitogen-activated protein kinase signaling controls basal and oncostatin M-mediated JUNB gene expression.
abstract: 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 MCF10A(met), SKBR3, and MDA-MB-231 human breast cancer cell lines compared to nontransformed MCF10A mammary epithelial cells. Increased RAS/MAPK signaling in MCF10A(met) 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.
authors: Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, OH, 43210, USA.
authors: Mellissa J
authors: MJ
authors: Hicks
authors: Qiuping
authors: Q
authors: Hu
authors: Erin
authors: E
authors: Macrae
authors: James
authors: J
authors: DeWille
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D053683:Oncostatin M / Q000494:pharmacology*; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002070:Butadienes; C581727:JunB protein, human; D009570:Nitriles; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; C113580:U 0126; D053683:Oncostatin M; D010768:Phosphoserine; D012319:RNA Polymerase II