title: Effects of parafibromin expression on the phenotypes and relevant mechanisms in the DLD-1 colon carcinoma cell line.
abstract: BACKGROUND
  Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells.
  
  
  METHODS
  DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays.
  
  
  RESULTS
  The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, GSK3β-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma.
  
  
  CONCLUSIONS
  Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.
authors.affiliation: Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University, JinZhou, China. zheng_huachuan @hotmail.com
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Sun
authors.forename: Shi-Tu
authors.initials: ST
authors.lastname: Zhu
authors.forename: Hang
authors.initials: H
authors.lastname: Lu
authors.forename: Zhe-Feng
authors.initials: ZF
authors.lastname: Niu
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Guo
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing; D055815:Young Adult
chemical_list: C454900:CDC73 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000469:Alkaline Phosphatase