NF-κB activation in mice with an IκBα mutation induces <i>IGF2</i> LOI in the mouse prostate.

<p>(A) Prostate tissues were dissected from informative male IκBα+/+ and IκBα+/− mice (1 mo) and RNA obtained. Maternal and paternal allelic expression was measured using FluPE. The ratio of the inactive allele (Ai) to active allele (Aa) was calculated for each age cohort (n = 15, *, <i>P</i><0.05). Increased LOI was demonstrated in the 1 mo mouse DLPs. (B) <i>IGF2</i> expression increases in 1-month IκBα+/− mouse DLPs. RT-qPCR was used to measure <i>IGF2</i> expression levels in the mouse DLPs of the 1 mo-old cohorts. Values are expressed as mean+/−S.D (n = 10, * <i>P</i><0.05). (C) CTCF expression decreases in 1-month IκBα+/− mouse DLPs. RT-qPCR was used to measure CTCF expression levels in the mouse DLPs of the 1 mo-old cohorts. Values are expressed as mean+/−S.D (n = 10, * <i>P</i><0.05). (D) Schematic of NF-κB and CTCF pathway. Hydrogen peroxide stimulates the activation of IKKβ, resulting in the phosphorylation of IκBα at Ser 32 and Ser 36. This leads to its degradation with release of the NF-κB (p65/p50 heterodimer) and subsequent translocation to the nucleus. NF-κB binds to the promoter region of CTCF, with the corepressor HDAC1 and reduces transcription of the CTCF gene. Decreased expression of CTCF results in DNA hypermethylation and <i>IGF2</i> LOI.