Morphoproteomic Confirmation of an Activated NF-Kappa B Pathway in Colorectal Adenocarcinoma
S Dhingra, RE Brown, AL Cota, J Xiao, T Lei, X Duan. The University of Texas-Houston, Medical School, Houston, TX
Background: The upregulation of interleukin 8 (IL 8) has been reported to be associated with induction, progression and metastatic potential of colorectal cancer. IL-8 is also a known transcriptional target of nuclear factor (NF)-kappa B and is overexpressed in a number of malignancies. In this study, we investigated the constitutive activation of the NF-kappa B pathway in colorectal adenocarcinoma (CAD) versus non-neoplastic colonic epithelium.
Design: A Tissue microarray with 30 primary colonic adenocarcinoma and 20 non-neoplastic colonic mucosa was assembled and immunostains were utilized for detection of IL-8, phosphorylated (p)-NF-kappaBp65 (Ser 536) and glutathione S transferase(GST)-pi. Chromogenic signal and cellular localization were assessed by bright field microscopy and the intensity of these signals was scored as (0-3+).
Results: Strong (2+ to 3+) IL-8 expression was observed in (28/30)97% of CAD tissues and the signal was predominantly perinuclear while non-neoplastic epithelium was essentially negative. p-NF-kappa Bp65 and GST-pi were expressed in all (100%) cases of cancer as well as non-neoplastic colonic epithelium tissue; however, the immunostaining was stronger (2+ to 3+) in CAD versus weak to 1+ in non-neoplastic tissue. The GST-pi localization was cytoplasmic and the p-NF-kappaBp65 was predominantly nuclear.
Conclusions: Morphoproteomic analysis reveals the activation of the NF-kappa B pathway in colorectal adenocarcinoma as evidenced by overexpression of NF-kappa Bp65 (Ser536) with nuclear translocation and parallel increases in expression of IL-8 and GST-pi. The perinuclear localization of IL 8 provides supportive evidence of the activation of NF-kappa B. This study confirms the activation of NF-kappa B pathway in the pathogenesis of CAD leading to transcriptional activation of IL-8 and GST-pi genes.
Monday, March 9, 2009 1:00 PM
Poster Session II # 83, Monday Afternoon