BMC Cancer 2009, 9:251 http://www.biomedcentral.com/1471-2407/9/251 4.19191 2.52900 3.36607 3.58972 Lower 95% CI** 34.60355 10.43976 54.65772 81.64806 Upper 95% CI** 51.06885 20.37384 67.87973 95.74819 Page 8 of 11 (page number not for citation purposes) BF-igcautreeni7n cellular localization in WT and CyCAP KO mice B-catenin cellular localization in WT and CyCAP KO mice. In WT mice, β-catenin expression is higher in the colonic plate than in the crypts of the colon mucosa (A). However, CyCAP KO mice show overall increased membra- nous expression of β-catenin with irregular distribution, which focally significantly extended into crypts (B). No defi- nite nuclear localization of β-catenin was detected either in WT or KO mice. colonic mucosal growth. Suzuki et al. [73] developed an experimental hyperplasia in nu/nu mice by transfer of lymphocytes from the C57BL/6 mice infected by murine leukemia virus (LP-BM5). Lymphocyte transfer to nu/nu mice induced colitis and hyperplasia of intestinal epithe- lial cells. In contrast to CyCAP mice in our study, which did not show any mucosal inflammation in addi- tion to the hyperplasia, these mice developed marked mononuclear infiltrates rich in CD4+/CD45RBlow T-cells. Suzuki et al. [73] work shows that in such model, hyper- plasia of the colon may be due to defects in immunoreg- ulatory mechanisms. TAA90K belongs to an ancient protein superfamily which is defined by a scavenger recep- tor cysteine-rich (SRCR) domain [41]. It is particularly noteworthy that all the previously characterized SRCR domains occur in proteins involved in or thought to par- ticipate in critical functions of the cellular host defense system, and thus they resemble the immunoglobulin superfamily of the cysteine-containing protein domains (reviewed in ref. 31). Histochemically, Mac-2 has been located intracellularly in many members of the macro- phage lineage, including tissue macrophages, certain den- dritic cells, alveolar and Kupffer cells [74,75]. Table 2: Independent Samples T-Test for Equality of Means Type 1 vs. 2 Type 3 vs. 4 Type 1 vs. 3 Type 2 vs. 4 < 0.0001 < 0.0001 < 0.0001 < 0.0001 42.83620 15.40680 61.26872 88.69812 * Animal type as per Table 1. ** Confidence Interval of the Difference Table 1: Distribution of Mean Thickness and SD of Non-Tumoral Colonic Mucosa Animal Type Type 1: WT + A Type 2: KO + A Type 3: WT Type 4: KO Mean (μm) 182.5761 225.4123 121.3074 136.7142 SD 48.53183 54.00269 30.88762 30.33236 SD = Standard Deviation, A = Azoxymethane, WT = Wild Type Mice, KO = Knock Out Mice enhancement of 90 K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cells, but by stimulation of the residual cell- mediated immune defense of the nude mouse. Recently, Rigby at al. [76] showed a role of suppressor of cytokine signaling-3 (SOCS3) in colonic mucosal epithe- lial proliferation. Mice with disrupted SOCS3 gene responded with increased proliferation and increased crypt depth after acute dextran sodium sulfate(DSS)- induced mucosal injury or after azoxymethane and chronic DSS. However, the authors did not report sponta- neously developing mucosal hyperproliferation and mucosal hyperplasia as it was the case in CyCAP deficient mice in our study. Similarly, Jones et al. [77] reported that conditional deletion of beta-1 integrins in the intestinal epithelium causes a loss of Hedgehog expression and intestinal hyperplasia. However, images illustrated in their publication reveal architectural abnormalities and cytologic atypia, both of which are indicating develop- ment of ectopic crypts and adenomas rather than simple lengthening of the crypts, which would indicate hyperpla- sia only. Wnt/β-catenin signalling is critically important for colon organogenesis and also for colon carcinogenesis. Wnt pro- tein binding to Frizzled (Fzd) and low-density lipoprotein receptor-related proteins (LRP) causes inactivation of gly- cogen synthase kinase (GSK) 3β and Axin, respectively. The inactivation of these proteins stabilizes β-catenin, which subsequently accumulates in the cell nucleus and activates the transduction of target genes that are crucial in the G1-S-phase transition and therefore, nuclear β-catenin Animal Type* Sig. (2-tailed) Mean Difference Std. Error Difference Importantly, Jallal et al. [23] showed that engineered co-localize with markers of proliferation including c-myc