title: Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer.
abstract: OBJECTIVE
  Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1.
  
  
  METHODS
  Levels of COX-2 and MUC1 were determined in MUC1(-/-), MUC1(low), and MUC1(high) PDA cells and tumors using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene.
  
  
  RESULTS
  Significantly higher levels of COX-2 mRNA and protein were detected in MUC1(high) versus MUC1(low/null) cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ∼1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor κB p65 associates with the COX-2 promoter.
  
  
  CONCLUSIONS
  Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients.
authors.affiliation: From the *Department of Biology, University of North Carolina at Charlotte, Charlotte; and †School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Sritama
authors.initials: S
authors.lastname: Nath
authors.forename: Lopamudra Das
authors.initials: LD
authors.lastname: Roy
authors.forename: Priyanka
authors.initials: P
authors.lastname: Grover
authors.forename: Shanti
authors.initials: S
authors.lastname: Rao
authors.forename: Pinku
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; C060192:MUC1 protein, human; D018396:Mucin-1; C498143:RELA protein, human; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human