The theory that PPARB encourages the induction of terminal differentiation is supported by data from numerous models including keratinocytes, abdominal epithelium, osteoblasts, oligodendrocytes, monocytes and in a variety of cancer models including colon, chest and neuroblastoma cells. This procedure requires the altered expression of gene products that inhibit cell proliferation, increased expression of gene products needed deubiquitinating enzyme inhibitors for terminal differentiation, and inhibition of cell proliferation, consequences that are not seen in cells lacking expression of PPARB. Considerable evidence also supports the theory that PPARB can restrict pro-inflammatory signaling. For example, more than fifty reports show that PPARB may prevent expression of pro-inflammatory signaling by decreasing the expression of TNF, IL1B, IL6 and MCP1. Several changes in the expression of pro inflammatory signaling proteins are thought to be mediated by direct inhibition of NF W dependent signaling, but PPARB dependent inhibition of STAT3 and AP1 phosphorylation has also been identified. As inflammation is from the growth of many cancers 106 and anti inflammatory drugs are recognized to effectively prevent some cancers, it is curious that no studies to date have specifically examined Endosymbiotic theory whether activating PPARB might prevent tumorigenesis by inhibiting inflammation. Given the potency of evidence that PPARB could mediate powerful anti inflammatory actions, detailed examination is warranted by this hypothesis. The event of PPAR in tumor growth is also controversial. You will find many published reports demonstrating that activating PPAR prevents cancer in tissues such as colon, breast, prostate, lung and many others. Indeed, the majority of studies so far show that PPAR agonists could encourage terminal differentiation, inhibit cell growth and increase apoptosis of human cancer cell lines, inhibit tumorigenesis in animal models of cancer, and in some cases PPAR agonists demonstrate modest efficacy for chemoprevention in clinical trials. similar to the retrospective study examining a relationship Icotinib between survival of colorectal cancer patients and expression of PPARB 60. This is consistent with results showing that colon tumorigenesis is exacerbated in APCmin mice with genetic ablation of Pparg compared with control APCmin mice 110. Ligand activation of PPAR in cancer cell lines is associated with induction of cell cycle arrest, elevated expression of mRNAs and proteins required for terminal differentiation including keratins, carcinoembryonic antigen, E cadherin, alkaline phosphatase and differentiation connected gene 1, as well as changes in cell morphology consistent with a differentiated phenotype 111 115. One procedure that may mediate PPAR dependent induction of terminal differentiation is via an interaction with HIC5, which may serve as a PPAR corp activator 116.