4.7 Article

African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression

Journal

CANCER LETTERS
Volume 380, Issue 2, Pages 513-522

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.06.025

Keywords

Kaiso; Pancreatic ductal carcinoma; EMT markers

Categories

Funding

  1. Department of Defense Prostate Cancer Research Program [PC120913]
  2. NIH/RCMI [G12 RR03059-21A1]
  3. NIH/NCI [1 R21 CA188799-01, U54 CM 18623]
  4. pilot project on Pancreatic SPORE [2 P50 CA101955-11]

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Kaiso, a bi-modal transcription factor, regulates gene expression, and is elevated in breast, prostate, and colon cancers. Depletion of Kaiso in other cancer types leads to a reduction in markers for the epithelial-mesenchymal transition (EMT) (Jones et al., 2014), however its clinical implications in pancreatic ductal adenocarcinoma (PDCA) have not been widely explored. PDCA is rarely detected at an early stage but is characterized by rapid progression and invasiveness. We now report the significance of the subcellular localization of Kaiso in PDCAs from African Americans. Kaiso expression is higher in the cytoplasm of invasive and metastatic pancreatic cancers. In males, cytoplasmic expression of Kaiso correlates with cancer grade and lymph node positivity. In male and female patients, cytoplasmic Kaiso expression correlates with invasiveness. Also, nuclear expression of Kaiso increases with increased invasiveness and lymph node positivity. Further, analysis of the largest PDCA dataset available on ONCOMINE shows that as Kaiso increases, there is an overall increase in Zeb1, which is the inverse for E-cadherin. Hence, these findings suggest a role for Kaiso in the progression of PDCAs, involving the EMT markers, E-cadherin and Zeb1. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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