Figure 5. Heterozygous IKK2ca expression in IECs strongly enhances tumorigenesis in Apc1638N mice and results in early tumor formation in the colon and the SI.

(A) Macroscopic analysis of intestines from 4-month-old mice showed that all Apc1638N/IKK2ca^IEChet mice examined (n = 11) had developed at least 1 macroscopically visible tumor in the colon and also multiple clearly identifiable polyps in the proximal half of the SI. Littermate Apc1638N/IKK2ca^sFL mice (n = 6) did not show colon tumors, while only 2 out of 6 animals examined bore 1 or 2 small polyps in the pyloric region of the SI. IKK2ca^sFL (n = 9) and IKK2ca^IEChet (n = 11) mice did not show tumors in either the colon or the SI. (B) Histological analysis of colon sections from Apc1638N/IKK2ca^IEChet mice revealed the presence of tumors showing hyperplastic and dysplastic crypts with multilayered undifferentiated epithelium. Histological analysis of proximal SI sections from Apc1638N/IKK2ca^IEChet mice revealed the growth of polyps that harbored aberrantly shaped, dysplastic crypts showing epithelial stratification and lack of differentiation. Histological analysis of colon and SI sections from IKK2ca^IEChet and IKK2ca^sFL littermates did not reveal the presence of tumors. (C) Immunostaining for Ki67 revealed increased proliferation of epithelial cells in adenomas from the colon and SI of Apc1638N/IKK2ca^IEChet mice, whereas Apc1638N/IKK2ca^sFL mice showed a normal Ki67 staining pattern. (D) Immunohistochemical analysis revealed strong Sox9 expression in all epithelial cells in colonic and SI tumors in Apc1638N/IKK2ca^IEChet mice. In contrast, Apc1638N/IKK2ca^sFL mice showed normal Sox9 staining, with Sox9-positive IECs in the base of the crypts and the transit-amplifying compartment in both tissues. Scale bars: 50 μm.