Anti-BCL10 monoclonal antibody, clone FQS9698

Background: Products of cyclin-dependent kinase inhibitor p16(IN2K4A) and mitotic arrest defective protein 2 (MAD2) genes are key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16(INK4A) and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). Materials and Methods: Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11; 18)(q21;q21) translocation. Results and Conclusion: p16(INK4A) was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16INK4A methylation tended to be negative for t(11; 18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16(INK4A) and MAD2 gene may play a role in the pathogenesis of MZBCL via different path ways; MAD 2 gene is Helicobacter pylori independent with a close association with BCL10 while p16(INK4A) is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation. Copyright (C) 2009 S. Karger AG, Basel

Many features of deadly human cervical cancers (HCCs) still require elucidation. Among HCC-derived cell lines, here we used the C4-I one since its quantitative gene expression pattern most closely mimics invasive HCCs, including protein kinase-C zeta (PKC zeta) overexpression. Via proteomic, bioinformatic, and biochemical approaches we identified 31 and 33 proteins co-immunoprecipitating with PKC zeta from nuclear membranes (NMs) of, respectively, untreated or VP-16-exposed C4-I cells. Such proteins belonged to eight functional groups, whose compositions and relative sizes changed with either context. Of the 56 proteins identified, only eight were shared between the two subproteomes, including Bcl10. Surprisingly, proteins known to associate with Bcl10, like Carma1/3 and Malt1, in so-called CBM signalosomes were absent. Notably, in VP-16-treated C4-I cells, PKC zeta center dot Bcl10 complexes increasingly accrued at NMs, where PKC zeta phosphorylated Bcl10, as PKC zeta also did in vitro and in cell-free systems, both processes being thwarted by interfering RNA (iRNA) PKC zeta depletion. Caspase-3 was associated with PKC zeta center dot Bcl10 complexes and proteolyzed PKC zeta leading to its inactivation/destruction; both events were prevented by Bcl10 iRNA suppression. Thus, PKC zeta's molecular interactions and functional roles changed strikingly according to the untreated or apoptogen-treated cells context, and by complexing with Bcl10, PKC zeta surprisingly favored its own demise, which suggests both proteins as HCCs therapeutic targets.