title: The hypoxia-mimetic agent cobalt chloride induces cell cycle arrest             and alters gene expression in U266 multiple myeloma cells.
abstract: Hypoxia is a common feature of tumors that occurs across a wide variety             of malignancies. Multiple myeloma is an incurable malignant disorder of plasma             cells in the bone marrow. Although bone marrow hypoxia is crucial for normal hematopoiesis,             the effect of hypoxia on multiple myeloma is poorly understood. In this study,             we demonstrated that cobalt chloride (CoCl2)-mediated hypoxia decreased cell viability             and altered gene expression in U266 human multiple myeloma cells. CoCl2 induced             the loss of cell viability in a concentration-dependent manner. In addition, FACS             analysis revealed that the loss of cell viability was related to apoptosis. Using             microarray analysis, we identified mRNA expression profile changes in response             to CoCl2 treatment in U266 cells. Four hundred and fifty-two mRNAs exhibited >2-fold             changes in expression in CoCl2-treated U266 cells compared to their expression             in control cells. A follow-up bioinformatics study revealed that a great number             of genes with altered expression were involved in apoptosis, cell cycle, transcription             and development. In conclusion, these results provide novel evidence that CoCl2-mediated             hypoxia affects the expression profiles of genes that are functionally related             to apoptosis and angiogenesis in U266 multiple myeloma cells.
authors.affiliation: Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu,                     Seoul 143-701, Republic of Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.forename: Karam
authors.initials: K
authors.lastname: Kim
authors.forename: Yeong Min
authors.initials: YM
authors.lastname: Choi
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.forename: Hyea Jung
authors.initials: HJ
authors.lastname: Koh
authors.forename: Dae Jin
authors.initials: DJ
authors.lastname: Lim
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003035:Cobalt / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome / Q000187:drug effects
chemical_list: D003035:Cobalt; C018021:cobaltous chloride