Dataset: IKKα promotes intestinal tumorigenesis

Depending on the tumor type IκB kinase α (IKKα) can act as tumor promoter or tumor suppressor in various malignancies. Here we demonstrate a key function of IKKα in the suppression of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of IFNγ expressing M1-like myeloid cells. In IKKα mutant mice M1-like polarization is not controlled in a cell autonomous manner but depends rather on the interplay of both IKKα mutant tumor epithelia and immune cells. Tamoxifen-inducible β-catc.a. mice comprise an excellent model to study Wnt-dependent tumor initiation. These mice are characterized by IEC-restricted stabilization of β-catenin causing rapid expansion of intestinal crypts and loss of differentiated IEC. To further explore the underlying IKKα controlled pro-proliferative mechanism, we performed a microarray analysis comparing RNA isolated from wildtype, IkkαAA/AA, β-catc.a. or β-catc.a./IkkαAA/AA IEC 15 days after the first tamoxifen administration. and within 4 weeks β-catc.a. mice succumb to this marked crypt hyperproliferation

Species:

mouse

Samples:

8

Source:

E-GEOD-51631

Updated:

Dec.12, 2014

Registered:

Nov.24, 2014