Increased Expression of DNA Repair Genes in Invasive Human Pancreatic Cancer Cells.
Mathews, Lesley A. PhD *; Cabarcas, Stephanie M. PhD *; Hurt, Elaine M. PhD +; Zhang, Xiaohu MD ++; Jaffee, Elizabeth M. MD [S][//]; Farrar, William L. PhD *
40(5):730-739, July 2011.
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Objective: Pancreatic cancer was the fourth leading cause of cancer death in the United States in 2010. Recurrence of disease after resection occurs because of neoplastic cell survival. To better understand these highly aggressive cells, gene expression microarrays were performed.
Methods: Using the established lines HPAC and PANC1 and a Matrigel assay, genome expression arrays were performed to analyze patterns between invasive and total cells.
Results: Significant increases in the expression of genes related to DNA repair were observed. A number of the same genes also demonstrated an increase in expression when comparing bulk cells to a putative tumor-initiating cell (TIC) population. The TIC population was isolated using the spheroid technique, and compared with bulk cells, spheroid cells functionally repair breaks in DNA faster after challenge with the drug gemcitabine. Finally, using Oncomine, we observed a significant increase in DNA copy number of BRCA1 and RAD51 in tissue isolated from metastatic pancreatic cancer compared with tissue isolated from the primary site.
Conclusions: From these data, we conclude that the most invasive cells within a pancreatic tumor are able to thrive because of their increased genomic stability. These cells have also been linked to the TIC population in a tumor.
(C) 2011 Lippincott Williams & Wilkins, Inc.