Fitzpatrick LR, Small JS, Poritz LS, McKenna KJ, Koltun WAEnhanced intestinal expression of the proteasome subunit low molecular mass polypeptide 2 in patients with inflammatory bowel disease. Dis Colon Rectum 50(3): 337-348

Department of Surgery, Section of Colon and Rectal Surgery, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
Diseases of the Colon & Rectum (Impact Factor: 3.75). 04/2007; 50(3):337-48; discussion 348-50. DOI: 10.1007/s10350-006-0796-7
Source: PubMed


Low molecular mass polypeptide 2 is an inducible immunoproteasome subunit. The expression of low molecular mass polypeptide 2 has not been examined in the intestine of patients with inflammatory bowel disease. This study was designed to determine whether the intestinal expression of low molecular mass polypeptide 2 was enhanced in a group of patients with inflammatory bowel disease compared with a group of control patients without inflammatory bowel disease. Moreover, we examined the association between low molecular mass polypeptide 2 expression and histologic pathology in these patients.
Twenty-one patients participated in the study. These included six control subjects without inflammatory bowel disease, eight patients with ulcerative colitis, and seven patients with Crohn's disease. Intestinal low molecular mass polypeptide 2 expression was evaluated by immunohistochemistry, as well as by Western blot. Histology scores (0-40 severity scale) were determined on the same sections of intestine as those used for low molecular mass polypeptide 2 histochemistry.
By immunohistochemistry, low molecular mass polypeptide 2 expression was significantly enhanced (P < 0.05 vs. control subjects) throughout visibly diseased areas of colon, rectum, and ileum from patients with inflammatory bowel disease. Low molecular mass polypeptide 2 expression also was increased in macroscopically normal intestine from patients with inflammatory bowel disease compared with normal tissue from control subjects. There was a significant correlation (P < 0.0001) between low molecular mass polypeptide 2 expression and histologic pathology in our patients. Western blot results confirmed that low molecular mass polypeptide 2 expression was enhanced in patients with ulcerative colitis (3.1-fold) and in patients with Crohn's disease (3.5-fold).
Intestinal low molecular mass polypeptide 2 expression is significantly increased in inflammatory bowel disease. The association between intestinal low molecular mass polypeptide 2 expression and histologic pathology suggests that this proteasome subunit plays a role in the pathogenesis of inflammatory bowel disease.

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    • "We found that a variety of solid cancer cell lines as well as patient prostate tumour tissues express high levels of LMP2. Given that LMP2 upregulation is implicated in several pathological disorders and that UK-101 inhibits the growth of prostate cancer cells (Fitzpatrick et al, 2007; Wehenkel et al, 2008), LMP2 may represent a novel drug target. Our knockdown studies indicate that depletion of the LMP2 subunit in PC-3 cells has a growth inhibitory effect, further supporting LMP2 as a novel target. "
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