Results and discussion Because the proteome directly affects phenotype, Bortezomib clinical trial but the transcriptome merely influences the proteome and thus may only indirectly affect the phenotype, we based our systems biology model of neoplastic transformation in MD on the differences between the transformed CD30hi, and the non transformed CD30lo MD lymphocytes proteomes. We isolated CD30hi and CD30lo lymphocytes directly ex vivo at 99% purity as described. All comparisons and differential expres sions are expressed as CD30hi relative to CD30lo lym phocytes. Of the 11,958 proteins we identified 1,588 proteins were significantly increased, and 808 proteins had significantly decreased expression in the CD30hi lymphocytes.
Functional modeling To visualize the Inhibitors,Modulators,Libraries differences between the CD30hi and CD30lo lymphocytes proteomes in terms of well studied cancer pathways, the differential protein ex pression data was manually mapped to the cancer specific pathway Pathways in cancer from the Kyoto Encyclopedia of Genes and Genomes. This specific KEGG pathway is a map of several different interacting signaling pathways and so provides a comprehensive overview of the mo lecular signatures of CD30hi and CD30lo lymphocyte proteomes. We further modified the KEGG pathway by adding the Meq oncoprotein, previously published Meq interacting proteins, and our hypothesized Meq CD30 NFB feed forward loop. A mixed pattern emerged Inhibitors,Modulators,Libraries with protein levels in creasing, decreasing and not changing. However, Inhibitors,Modulators,Libraries in several of the pathways described below, key regula tory proteins were differentially expressed, NFB, IKK, VEGF, MDM2, CD30, HSPA2, MYC, JUN, TGFB, and Meq were increased, whereas, RB, PENK, and BRCA2 were decreased.
This indicates that neoplastic transformation is being regulated by these key Inhibitors,Modulators,Libraries pro teins. The MDV oncoprotein Meq interactions, and our hypothesized Meq CD30 NFB feed forward loop, suggest that Meq interacts with several key proteins involved in neoplastic transformation, immune evasion and cell survival. Ingenuity Pathway Analysis based functional Inhibitors,Modulators,Libraries grouping of the significantly expressed pathways confirmed our pre vious findings that PCD was perturbed and integrin signaling was increased in CD30hi cells. IPA analysis also indicated that PCD signaling, molecular mechanisms of cancer, NFB activation by viruses, p53 signaling, PPAR RXR activation, PTEN signaling, BRCA1 in DNA damage, VEGF signaling, selleck Wnt B catenin signaling, lymphotoxin B receptor signaling, TGF B signaling and nitric oxide signaling were acti vated in both CD30hi and CD30lo cells.