title: The role of the WWOX gene in leukemia and its mechanisms of action.
abstract: The WW domain-containing oxidoreductase (WWOX) gene which encompasses the common human fragile site FRA16D has been proposed as a putative tumor suppressor gene, and loss of WWOX expression has been found in several types of solid cancer. As the role of WWOX in human leukemia has not yet been fully elucidated, the present study examined the expression of WWOX in patients with different types of leukemia as well as in leukemia-derived cell lines. Based on the data, WWOX mRNA (WWOX) and protein (Wwox) were significantly reduced or absent in the leukemia patients as well as in the cell lines. In addition, a recombinant expression vector, pGC-FU-WWOX, was constructed and transfected WWOX cDNA into Jurkat cells (acute T-lymphoblastic leukemia) and K562 cells (chronic myeloid leukemia in erythroid crisis) which all lack endogenous Wwox. In vitro experiments indicated that restoration of Wwox in Jurkat and K562 cells significantly suppressed proliferation and colony formation. Of note, apoptosis was also induced by Wwox restoration. Furthermore, we traced the mechanisms underlying this process and found that Wwox restoration could trigger the mitochondrial pathway in leukemia. Our data provide evidence that WWOX exerts a role as a tumor suppressor gene in leukemia, possibly by inhibiting proliferation and promoting apoptosis via the mitochondrial pathway.
authors.affiliation: Department of Clinical Laboratory, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian 350004, PR China. cuileidizi@163.com
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Cui
authors.forename: Donghong
authors.initials: D
authors.lastname: Lin
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Lingqing
authors.initials: L
authors.lastname: Luo
authors.forename: Lingying
authors.initials: L
authors.lastname: Kong
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.forename: Jianda
authors.initials: J
authors.lastname: Hu
authors.forename: Fenghua
authors.initials: F
authors.lastname: Lan
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000074584:WW Domain-Containing Oxidoreductase; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9