The Actual ROR1 All Your Co-Workers Is Speaking Of

In order to investigate this key gene family in human prostate cancer, we used ten prostate cancer gene expression datasets (Table S1) to construct a single prostate cancer-specific functional network (see Methods); the entire process of querying, downloading, normalizing, standardizing and integrating these datasets took MK-2206 purchase genes in BioCarta (see Methods, Table S4). This query process retrieved seven additional genes known from prior work to be involved in NF��B ROR1 signaling (Davis, Kucuk & Sarkar, 1999; Perkins, 2012) (Fig. 2): Tumor protein p53 (TP53), TNF receptor-associated factor 2 (TRAF2), receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1), mitogen-activated protein kinases (MAP3K14 and MAP2K1), and interleukins (IL1B and IL10). Two newly-associated genes with potential relationships to NF��B and prostate cancer were also recovered: Menin (MEN1) and acyl-CoA binding domain containing 6 (ACBD6). MEN1 is a putative tumor suppressor known to physically interact with NF��B proteins (Heppner et al., 2001). Here, we observed that in prostate cancer, MEN1 was significantly co-expressed with TP53 and I��B kinase (IKK), specifically the gamma subunit (Fig. 2). The I��B complex phosphorylates NF��B to activate the cellular response to inflammation (Bouwmeester et al., 2004; Hacker & Karin, 2006; Wen et al., 2000), suggesting that MEN1 may represent a novel upstream regulator of the pathway in prostate cancer. ACBD6 is a poorly-characterized protein that has been implicated in few specific areas; one of these is growth of Chlamydia trachomatis, for which it is essential in cell culture (Soupene et al., 2012). C. trachomatis has been implicated as a microbial driver in prostate carcinogenesis and has also been shown to elicit chemokine production from immune cells and non-immune cells isolated from the prostate (Oberti et al., 2011). Our prediction Selleck ABT-263 suggests a more specific role for ACBD6 in prostate cancer as a potential suppressor of NF��B activity and downstream inflammation, as it was highly co-expressed with the two NF��B inhibitors, NF��B IA and NF��BIE (Pringle et al., 2012; Wu et al., 2006) (Fig. 2). This hypothesis is consistent with ACBD6��s previously-reported role in bacterial growth if it represents one mechanism by which the antimicrobial response is repressed through suppression of NF��B.