{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nath S"],"funding":["NCI NIH HHS"],"pagination":["909-17"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4500655"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(6)"],"pubmed_abstract":["<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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."],"journal":["Pancreas"],"pubmed_title":["Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer."],"pmcid":["PMC4500655"],"funding_grant_id":["R01 CA118944-01A1","R01 CA118944"],"pubmed_authors":["Rao S","Mukherjee P","Nath S","Roy LD","Grover P"],"additional_accession":[]},"is_claimable":false,"name":"Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer.","description":"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Aug","modification":"2024-11-14T09:50:41.303Z","creation":"2019-03-27T01:55:03Z"},"accession":"S-EPMC4500655","cross_references":{"pubmed":["26035123"],"doi":["10.1097/MPA.0000000000000371"]}}