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.
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Acknowledgements
We are grateful to George Elia and members of the Cancer Research UK Histopathology Laboratory for technical assistance; Nick Hathaway, Steve Keirnan and Susan van Noorden of the Department of Histopathology, Hammersmith Hospital for help with tissue sectioning. Work was supported by grants from Cancer Research UK, Hammer Cancer, Hammersmith Hospitals Special Trustees, as well as (to A Scarpa) Associazione Italiana Ricerca Cancro, Milan, Italy and Ministero Università Cofin MM06158571, Rome, Italy.
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Crnogorac-Jurcevic, T., Efthimiou, E., Nielsen, T. et al. Expression profiling of microdissected pancreatic adenocarcinomas. Oncogene 21, 4587–4594 (2002). https://doi.org/10.1038/sj.onc.1205570
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DOI: https://doi.org/10.1038/sj.onc.1205570
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