fig3: Chicken ovalbumin upstream promoter-transcription factor II regulates metastasis of colon cancer in vivo in mice. Wild-type (WT) or COUP-TFII−/− mice were used to generate DMH/DSS-induced colon cancer models. (A) Typical appearance of metastatic foci on control livers (arrows). (B) Number of metastatic foci from A were calculated. *P<0.01 compared to WT. (C) Haematoxylin and eosin (H&E) staining for liver tissue. The arrow shows the tumour. Bar, 200 μm. (D) Immunohistochemistry was used to evaluate expression of E-cadherin and β-catenin from collected colon adenocarcinoma tissues. Bar, 50 μm. (E) Western blot showing expression of MMP2 and MMP9 in tumours from wild-type mice (WT) or COUP-TFII−/− mice (COUP-TFII−/−). (F) Control LOVO cells (CON) or COUP-TFII-depleted LOVO cells (COUP-TFII KD) were injected into spleens of nude mice. After 30 days, mice were killed and metastatic foci (arrows) on livers were examined. (G) Number of metastatic foci from F was calculated. *P<0.01 compared to CON. (H) H&E staining for liver tissue. Bar, 200 μm.

Mentions: To study COUP-TFII function in vivo, we generated COUP-TFII knockout mice by using tamoxifen-inducible knockout system (Xie et al, 2011) and used them as DMH/DSS-induced mouse models of colonic carcinogenesis. Body weight was slightly decreased in DMH/DSS-treated mice compared to normal mice. The body weight of COUP-TFII−/− mice (n=10, 5 male and 5 female) was not different than COUP-TFII+/+ mice. There was no difference between male and female mice. In both control and COUP-TFII−/− mice, the incidence of tumours was 100% and the incidence of colorectal tumours was similar (Table 2). Metastatic tumours in the liver were observed in COUP-TFII+/+ mice treated with DMH/DSS after 40 weeks (Figure 3A). No metastatic tumours were found in the livers of COUP-TFII−/− mice treated with DMH/DSS, suggesting that COUP-TFII was crucial for colon cancer metastasis, not for the formation of tumours.