title: Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphoma.
abstract: OBJECTIVE
  ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL.
  
  
  METHODS
  First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity.
  
  
  RESULTS
  ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3β. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway.
  
  
  CONCLUSIONS
  Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL.
authors.affiliation: a Department of Pathology , Affiliated Cancer Hospital of Nantong University , Nantong , PR China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Yin
authors.affiliation: b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China.
authors.forename: Qiru
authors.initials: Q
authors.lastname: Wang
authors.affiliation: b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ding
authors.affiliation: a Department of Pathology , Affiliated Cancer Hospital of Nantong University , Nantong , PR China.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D000072199:ADAM12 Protein / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor; D002448:Cell Adhesion / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D000072199:ADAM12 Protein
keywords: ADAM12; AKT/PI3K signaling pathway; CAM-DR; cell proliferation NHL