B-cell lymphoma model showed that HIF-1alpha promoted tumor growth; loss of 1 Hif1a allele in Tp53 deficient mice decreased the incidence of thymic lymphomas with delayed onset; and enhanced cell death was noted in Hif1a KO mice. These data assistance our findings, and this HIF1A TG model will supply important info relative to occurrence and improvement of lymphoma. Marzec et al reported that NPM/ALK chimeric gene, a causative gene abnormality in anaplastic massive cell lymphoma (ALCL) in humans, induced up-regulation of HIF-1alpha in T cell lymphoma cells [32]. The lymphoma cells detected in our HIF1A TG mice showed T cell phenotype determined by FCM and clonal rearrangement of T cell receptors concomitant with an increase of angiogenesis in tumor tissues. Furthermore, we obtained preliminary benefits displaying overexpression of HIF-1alpha in tumor tissues of human angioimmunoblastic T cell lymphoma (AITL). Given that VEGF expression along with a marked enhance of compact vessels in tumor tissue are prevalent options in AITL, HIF-1alpha may perhaps play an important role in tumorigenesis with the lymphoma in humans.PLOS One | www.plosone.orgDevelopment of Lymphoma by HIF-1alphaSupporting InformationFigure S1 Hematopoietic potential of HIF1A TG mice. (A) Serum concentration of erythropoietin in HIF1A TG or wild mice. (B) Complete blood counts of BALB/c, wild variety, heterogygous or homogygous transgenic mice.Cefditoren (Pivoxil) (C) In vitro colony-forming assays have been carried out in duplicate by plating 500 bone marrow cells with 1 ml of MethoCultTM M3434 medium, as described in Materials and Solutions.Phosphatidylserine Colonies were counted immediately after 4 days. (TIF) Figure S2 Fluorescence-activated cell sorter (FACS) analysis. Lymphocytes from spleen (A), thymocytes, (B) obtained from 6-month-old mice were counted and stained with fluorochrome-conjugated monoclonal antibodies working with regular procedures. Antibodies have been anti-mouse against CD3e, CD4, CD8, CD19, B220, CD25, CD44, IgM (eBiosciences). (PPTX)Table S1 Gene expression profile in lymphocytes obtained from TG mouse spleen. (DOCX)AcknowledgmentsWe thank Dr Shinji Fujimoto at Kyoto University for technical advices to conduct PCR evaluation on immunoglobulin and T cell receptor genes.PMID:23849184 We also thank Dr. Keiko Hiyama and Dr. Eiso Hiyama at Hiroshima University for technical advices to perform gene expression analyses, Donna F. Kusewitt for consultation on histological diagnosis, and Dr. Lorenz Poellinger at Karolinska Institute for offering HIF-1alpha expression plasmid and advices by means of this study.Author ContributionsConceived and developed the experiments: ES NS-A KT. Performed the experiments: ES NS-A AS MI HN YK KT. Analyzed the data: TK KN SK. Contributed reagents/materials/analysis tools: YS CT HY. Wrote the paper: ES NS-A KT.
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 289, NO. 25, pp. 17680 7688, June 20, 2014 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published inside the U.S.A.A Novel Ste20-related Proline/Alanine-rich Kinase (SPAK)independent Pathway Involving Calcium-binding Protein 39 (Cab39) and Serine Threonine Kinase with No Lysine Member four (WNK4) within the Activation of Na-K-Cl Cotransporters*Received for publication, December four, 2013, and in revised kind, April 7, 2014 Published, JBC Papers in Press, May perhaps 8, 2014, DOI 10.1074/jbc.M113.Jose Ponce-Coria, Nicolas Markadieu, Thomas M. Austin1, Lindsey Flammang, Kerri Rios, Paul A. Welling and Eric Delpire2 From the Department of Anesthesiology, Vanderbilt University Scho.