title: Expression profiling of microdissected pancreatic adenocarcinomas.
abstract: Pancreatic ductal adenocarcinoma is characterized by a paucity of neoplastic cells embedded in a densely desmoplastic stroma. Therefore, laser capture microdissection was performed to obtain homogeneous populations of normal and neoplastic ductal cells. These were subjected to a comparative study of gene expression utilizing human cDNA arrays. A variety of dysregulated genes were identified, comprising cell cycle and growth regulators, invasion regulators, signalling and developmental molecules. In addition to genes already found to be overexpressed in pancreatic cancer, such as TIMP1, MMP7, CD59, rhoC and NDKA, we present evidence to implicate genes which have not previously been reported in this tumour type. These include the overexpressed genes ABL2, Notch4 and SOD1, as well as XRCC1, a DNA repair gene whose transcript was found downregulated. Quantitative real-time RT-PCR (QRT-PCR) was employed to confirm differential expression of ABL2, Notch4 and SOD1 and immunohistochemical analysis was used to verify decreased protein expression of XRCC1 using a custom-built pancreatic tissue array. Combining microarray-derived gene expression profiles of pure pancreatic cell populations, QRT-PCR and pancreas-specific tissue arrays therefore proved to be highly informative in elucidating the molecular pathology of this highly malignant tumour type.
authors.affiliation: Cancer Research UK Molecular Oncology Unit, Imperial College School of Medicine at Hammersmith Campus, London, UK.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Crnogorac-Jurcevic
authors.forename: Evangelos
authors.initials: E
authors.lastname: Efthimiou
authors.forename: Torsten
authors.initials: T
authors.lastname: Nielsen
authors.forename: Julie
authors.initials: J
authors.lastname: Loader
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
authors.forename: Gordon
authors.initials: G
authors.lastname: Stamp
authors.forename: Antonella
authors.initials: A
authors.lastname: Baron
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Lemoine
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004210:Dissection; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm