The proliferative and survival effects of IL-6 on IEC are largely mediated by the transcription factor Stat3 [38] as mice lacking Stat3 in colonic epithelium develop fewer adenomas in spite of the fact that they have more severe colitis following exposure to AOM-DSS [38].
Conversely, mice that overexpress EDA in the epithelium develop an extra tooth in front of the molars (23).
Using intestinal epithelial cell-specific knockouts of Hif1α and Hif2α it was demonstrated that Hif2α is required for iron absorption, as mice lacking Hif2α in the intestinal epithelium developed a marked iron deficiency, characterized by low liver and serum iron levels [ 84].
In addition, transgenic mice overexpressing IL-1 α in gingival epithelium developed a periodontitis-like syndrome, leading to loss of attachment and destruction of alveolar bone [ 74].
Similarly, mice with targeted inactivation of Lkb1 in endometrial epithelium develop highly invasive (yet paradoxically extremely well-differentiated) endometrial adenocarcinomas [11].
We showed that mice carrying a targeted disruption of Brca1 in mammary epithelium developed mammary tumors at low frequency after long latency and the tumorigenesis was significantly accelerated in a p53+/- genetic background.
Additionally, mice that are null for Mst1 and Mst2 in the intestinal epithelium develop adenomas in the distal colon and possess an expanded undifferentiated stem cell compartment throughout their intestines [83].
Likewise, the outgrowths of E+P-treated Trp53+/- mammary epithelium developed tumors with frequency and latency similar to those of the Trp53+/- transplants from nulliparous mice.
However, a possible contamination of the mouse mesenchyme by mouse epithelium makes the interpretation uncertain.
The ApcΔ716 mouse develops ∼300 polyps, Apc1638N mouse develops ∼3, ApcΔ14 mouse develops ∼65, Apc mouse develops ∼35, ApcΔ580 mouse develops ∼120, and ApcΔ474 mouse develops ∼30 [16].
