Rabbit Anti-Human RUVBL1 (internal) Polyclonal antibody

Background: Progression of conventional urothelial carcinoma of the bladder to a tumor with unique microscopic features referred to as micropapillary carcinoma is coupled with aggressive clinical behavior signified by a high propensity for metastasis to regional lymph nodes and distant organs resulting in shorter survival. Objective: To analyze the expression profile of micropapillary cancer and define its molecular features relevant to clinical behavior. Design, setting, and participants: We retrospectively identified 43 patients with micropapillary bladder cancers and a reference set of 89 patients with conventional urothelial carcinomas and performed whole-genome expression messenger RNA profiling. Outcome measurements and statistical analysis: The tumors were segregated into distinct groups according to hierarchical clustering analyses. They were also classified according to luminal, p53-like, and basal categories using a previously described algorithm. We applied Ingenuity Pathway Analysis software (Qiagen, Redwood City, CA, USA) and gene set enrichment analysis for pathway analyses. Cox proportional hazards models and Kaplan-Meier methods were used to assess the relationship between survival and molecular subtypes. The expression profile of micropapillary cancer was validated for selected markers by immunohistochemistry on parallel tissue microarrays. Results and limitations: We show that the striking features of micropapillary cancer are downregulation of miR-296 and activation of chromatin-remodeling complex RUVBL1. In contrast to conventional urothelial carcinomas that based on their expression can be equally divided into luminal and basal subtypes, micropapillary cancer is almost exclusively luminal, displaying enrichment of active peroxisome proliferator-activated receptor gamma and suppression of p63 target genes. As with conventional luminal urothelial carcinomas, a subset of micropapillary cancers exhibit activation of wild-type p53 downstream genes and represent the most aggressive molecular subtype of the disease with the shortest survival. The involvement of miR-296 and RUVBL1 in the development of micropapillary bladder cancer was identified by the analyses of correlative associations of genome expression profiles and requires mechanistic validation. Conclusions: Micropapillary cancer evolves through the luminal pathway and is characterized by the activation of miR-296 and RUVBL1 target genes. Patient summary: Our observations have important implications for prognosis and for possible future development of more effective therapies for micropapillary bladder cancer. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Pontin, a member of the AAA+ ATPase family, plays important roles in a variety of cellular processes, including transcription regulation, DNA damage response, telomerase activity, and cellular transformation. In the previous studies, Pontin deletion in mice was lethal to embryos. Here, we demonstrate that the depletion of Pontin induced cellular senescence in mouse and human fibroblasts as well as in mouse epidermal keratinocytes. Fibroblast cells with Pontin depletion exhibited a defect in cell proliferation without showing apoptosis. Instead, they exhibited senescence-associated phenotypes including increased senescence-associated-beta-galactosidase activity, elevated levels of p16(INK4), and senescence-associated secretory phenotypes. Furthermore, conditional deletion of the Pontin gene in epidermal keratinocytes led to abnormal epidermal stratification, which was accompanied by the induction of senescence in Pontin-lacking cells. We found that Pontin depletion induced a spontaneous DNA damage response, which may be a cause of senescence. Contrary to the behavior of normal cells, Pontin depletion in several cancer cells caused apoptotic cell death without exhibiting senescence phenotypes.