title: Overexpression of ecdysoneless in pancreatic cancer and its role in oncogenesis by regulating glycolysis.
abstract: OBJECTIVE
  To study the expression and function of a novel cell-cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer pathogenesis.
  
  
  METHODS
  Immunohistochemical expression profiling of Ecd was done in nonneoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in pancreatic cancer progression, Ecd was stably knocked down in pancreatic cancer cell line followed by in vitro and in vivo functional assays.
  
  
  RESULTS
  Normal pancreatic ducts showed very weak to no Ecd expression compared to significant positive expression in pancreatic cancer tissues (mean ± SE composite score: 0.3 ± 0.2 and 3.8 ± 0.2 respectively, P < 0.0001) as well as in PanIN precursor lesions with a progressive increase in Ecd expression with increasing dysplasia (PanIN-1-PanIN-3). Analysis of matched primary tumors and metastases from patients with pancreatic cancer revealed that Ecd is highly expressed in both primary pancreatic tumor and in distant metastatic sites. Furthermore, knockdown of Ecd suppressed cell proliferation in vitro and tumorigenicity of pancreatic cancer cells in mice orthotopic tumors. Microarray study revealed that Ecd regulates expression of glucose transporter GLUT4 in pancreatic cancer cells and was subsequently shown to modulate glucose uptake, lactate production, and ATP generation by pancreatic cancer cells. Finally, knockdown of Ecd also reduced level of pAkt, key signaling molecule known to regulate aerobic glycolysis in cancer cells.
  
  
  CONCLUSIONS
  Ecd is a novel tumor-promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
authors.forename: Parama
authors.initials: P
authors.lastname: Dey
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Rachagani
authors.forename: Subhankar
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhao
authors.forename: Channabasavaiah Basavaraju
authors.initials: CB
authors.lastname: Gurumurthy
authors.forename: Judy M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Subodh
authors.initials: S
authors.lastname: Lele
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Vimla
authors.initials: V
authors.lastname: Band
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000556:secondary; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; C513410:ECD protein, human; D051275:Glucose Transporter Type 4; C495692:SLC2A4 protein, human; D005947:Glucose