title: Aberrant expressions of AP-2α splice variants in pancreatic cancer.
abstract: OBJECTIVE
  The present study was conducted to evaluate the expression and function of AP-2α isoforms in pancreatic ductal adenocarcinoma.
  
  
  METHODS
  The expression of AP-2α was evaluated at the RNA level by reverse transcription-polymerase chain reaction and at the protein level by Western blotting and immunofluorescence. Its function as a transcription factor was evaluated in transient transfection experiments: DNA binding properties by electromobility shift assay and transactivation capabilities by luciferase assay.
  
  
  RESULTS
  Multiple alternative splicing events of AP-2α messenger occurred in all human pancreatic cancer cell lines, including a novel isoform, termed variant 6, which was not present in HeLa cells. At the protein level, except for 1 cell line, all pancreatic cancer cell lines expressed high nuclear levels of AP-2α. We also showed that AP-2α expressed by the pancreatic cancer cell lines could bind its cognate recognition site and activate transcription. However, variant 6, although not able to activate transcription, did not act in a dominant negative manner when cotransfected with the full-length protein.
  
  
  CONCLUSIONS
  Multiple isoforms of AP-2α are highly expressed in pancreatic cancer cell lines including a new isoform, AP-2α variant 6, which seems to be pancreatic cancer specific and is deprived of transcriptional activity.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Hanover, NH, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Carrière
authors.forename: Sarah
authors.initials: S
authors.lastname: Mirocha
authors.forename: Sophie
authors.initials: S
authors.lastname: Deharvengt
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gunn
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D050656:Transcription Factor AP-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D050656:Transcription Factor AP-2