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The high frequency of chemotherapy resistance is ultimately responsible for clinical relapse in acute lymphoblastic leukemia (ALL). Nevertheless, the molecular mechanism relevant to glucocorticoid (GC) resistance remains ambiguous. Quantitative real-time polymerase chain reaction and Western blot were performed to detect the expressions of paraoxonase 2 (PON2), Bcl-2 and Bax. shRNA was used to knockdown PON2 expression in SUP-B15 and REH cell. CCK-8 and flow cytometry assay were conducted to monitor the changes of proliferation and apoptosis in ALL cells. The growth of ALL REH cells in vivo was determined using transplanted tumor model. This study was designed to identify GC resistance-associated genes by means of the transcriptome chip from the public Gene Expression Omnibus database, and preliminarily investigation of dexamethasone (DEX)-resistance mechanism in ALL. We disclosed that PON2 expression was elevated in ALL patients and especially higher in DEX-resistance ALL patients. Then, cell apoptosis assay suggested that silencing of PON2 dramatically promoted in DEX-resistant ALL cells apoptosis and the activity of Caspase 3 induced by DEX administration. In xenograft tumor model, PON2 knockdown significantly reduced DEX-resistant ALL cells growth in immunodeficient mice. Collectively, inhibition of PON2 may represent a novel method to restore the sensitivity of treatment-resistant ALL to GC-induced cell death. [ABSTRACT FROM AUTHOR]

Formation of the blastocoel in early Xenopus embryos was studied with a novel biotin-permeability assay and newly generated tight junction markers. The blastocoel forms at the first cleavage division since functional tight junctions which excluded biotin and established a segregated intraembryonic compartment were found at the 2-cell and all subsequent developmental stages. Unexpectedly, tight junctions before the 64-cell stage were not at their normal apical positions, but were found deep in the embryos, up to 200 [[micro]meter] from the apical surface. In these positions, the tight junctions left large areas of ion permeable lateral membranes exposed to the extraembryonic environment, explaining why electrophysiological experiments record a decrease in embryonic input resistances concomitant with early cleavage stages. Immunohistochemistry revealed that the recessed tight junctions did not influence the distribution of C-cadherin and [Na.sup.+], [K.sup.+]ATPase. Both markers were present apical to recessed tight junctions, indicating that the maintenance of polarization of these basolateral markers does not require tight junctions. With further development, tight junctions assumed an increasingly apical location until, by the 2000-cell stage, they occupied their conventional positions between the blastomeres at the apical/lateral membrane boundaries.

Abstract Background Neuronal synaptic junction protein δ-catenin (CTNND2) is often overexpressed in prostatic adenocarcinomas but the mechanisms of its activation are unknown. To address this question, we studied the hypothesis that Hes1, human homolog of Drosophila Hairy and enhancer of split (Hes) 1, is a transcriptional repressor of δ-catenin expression and plays an important role in molecular carcinogenesis. Results We identified that, using a δ-catenin promoter reporter assay, Hes1, but not its inactive mutant, significantly repressed the upregulation of δ-catenin-luciferase activities induced by E2F1. Hes1 binds directly to the E-boxes on δ-catenin promoter and can reduce the expression of δ-catenin in prostate cancer cells. In prostate cancer CWR22-Rv1 and PC3 cell lines, which showed distinct δ-catenin overexpression, E2F1 and Hes1 expression pattern was altered. The suppression of Hes1 expression, either by γ-secretase inhibitors or by siRNA against Hes1, increased δ-catenin expression. γ-Secretase inhibition delayed S/G2-phase transition during cell cycle progression and induced cell shape changes to extend cellular processes in prostate cancer cells. In neuroendocrine prostate cancer mouse model derived allograft NE-10 tumors, δ-catenin showed an increased expression while Hes1 expression was diminished. Furthermore, E2F1 transcription was very high in subgroup of NE-10 tumors in which Hes1 still displayed residual expression, while its expression was only moderately increased in NE-10 tumors where Hes1 expression was completely suppressed. Conclusion These studies support coordinated regulation of δ-catenin expression by both the activating transcription factor E2F1 and repressive transcription factor Hes1 in prostate cancer progression.

Abstract Background δ-Catenin is a unique member of β-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, δ-catenin is upregulated in human prostatic adenocarcinomas, although the effects of δ-catenin overexpression in prostate cancer are unclear. We hypothesized that δ-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival. Results We employed gene transfection and small interfering RNA to demonstrate that increased δ-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. δ-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of δ-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. δ-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, δ-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1. Conclusion Taken together, our studies suggest that at least one consequence of an increased expression of δ-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.