title: TRIB3 protein denotes a good prognosis in breast cancer patients and is associated with hypoxia sensitivity.
abstract: BACKGROUND
  Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survival after hypoxia and/or radiotherapy.
  
  
  METHODS
  TRIB3 mRNA and protein were quantified in a new independent breast cancer patient cohort using QPCR and a new specific avian antibody against TRIB3. In addition, we used siRNA-mediated knockdown of TRIB3 in a colony-forming assay after hypoxia and radiotherapy.
  
  
  RESULTS
  TRIB3 mRNA and protein levels did not correlate in breast cancer cell lines or human breast cancer material. We validated our earlier finding that high TRIB3 mRNA denotes a poor prognosis, but found that high TRIB3 protein levels were associated with a good prognosis in breast cancer patients. We also show that knockdown of TRIB3 resulted in an increased survival under hypoxic conditions.
  
  
  CONCLUSIONS
  Whereas mRNA levels of TRIB3 are related with a poor prognosis, TRIB3 protein is associated with a good prognosis in human breast cancer patients, possibly due to the fact that TRIB3 is involved in hypoxia tolerance.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands. M.Wennemers@labgk.umcn.nl
authors.forename: Marloes
authors.initials: M
authors.lastname: Wennemers
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Nicolai
authors.initials: N
authors.lastname: Grebenchtchikov
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases