Gain of Expression of Aldo-Ketoreductase Family 1 B10 (AKR1B10) Protein in Pancreatic Adenocarcinoma: A Potential Therapeutic Target.
Kristina A Matkowskyj, Jie Liao, Haonan N Li, Xianzhong Ding, M Sambasiva Rao, Guang-Yu Yang. Northwestern University, Chicago, IL
Background: Aldo-keto reductase family 1 B10 (AKR1B10) protein acts as an enzyme capable of reducing aliphatic aldehydes and ketones; it detoxifies reactive free radical carbonyl compounds and is involved in retinoid metabolism, thus modulating cell proliferation, differentiation and tumorigenesis. Expression of AKR1B10 protein is normally expressed in the intestine and over-expressed in liver and lung carcinomas. Several studies have identified upregulation of AKR1B10 in the normal respiratory epithelium of smokers, suggesting cigarette smoking as an inciting event. The development of pancreatic cancer is firmly linked to cigarette smoking, however the role of AKR1B10 in pancreatic ductal adenocarcinoma is not known. Here, we studied the expression of AKR1B10 in pancreatic epithelium and showed increased expression in pancreatic ductal adenocarcinomas.
Design: Normal and tumor pancreatic tissue microarrays were created for immunohistochemistry use and included 36 cases of pancreatic ductal adenocarcinoma and adjacent non-neoplastic pancreatic tissue from Whipple resection specimens. Immunohistochemistry was performed using a monoclonal mouse AKR1B10 antibody and the avidin-biotin-peroxidase approach. The staining intensity was classified as no staining or increased expression.
Results: AKR1B10 was expressed as cytoplasmic staining in pancreatic ductal adenocarcinoma compared to adjacent non-neoplastic pancreatic tissue. Increased expression of AKR1B10 was identified in 64% (n=23) of pancreatic ductal adenocarcinomas. The majority of the tumors expressing AKR1B10 were well and moderately differentiated (65 and 30%, respectively). In addition, 70% (n=16) of the tumors expressing AKR1B10 were identified to be from patients with a smoking history.
Conclusions: The over-expression of AKR1B10 in well and moderately differentiated pancreatic adenocarcinomas demonstrates that AKR1B10 may contribute to disease development via effects of smoking by altering retinoid homeostasis with dysregulated apoptosis and cellular proliferation, and should be considered as a candidate for further therapeutic investigations.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 66, Tuesday Afternoon