title: Expression of the apoptosis repressor with caspase recruitment domain (ARC) in liver metastasis of colorectal cancer and its correlation with DNA mismatch repair proteins and p53.
abstract: BACKGROUND
  Apoptotic signaling is one of the most important processes in the measurement of chemotherapeutic effectiveness. In apoptotic machinery, various pathways and proteins are involved (i.e., mismatch repair proteins, p53). One of the regulatory proteins is ARC, which can inhibit not only the extrinsic but also the intrinsic apoptotic signaling.
  
  
  METHODS
  In this study, we investigated the expression levels of ARC in colorectal liver metastasis and compared them with the expression of mismatch repair proteins and p53. Furthermore, we investigated ARC expression level depending on sex, age, tumor grade, mucin production, tumor size and number of liver metastasis.
  
  
  RESULTS
  ARC expression level in colorectal cancer liver metastasis was independent from clinical data (i.e., age, gender, tumor size, tumor number or mucin production) but strongly correlated with MSH2 and MSH6 expression, which further supported the evidence for the regulatory role of MSH2 and MSH6 in apoptosis; i.e., in case of sufficient MSH2 and MSH6 expression, significantly higher ARC level is required to suppress the apoptosis. A regulatory interaction between ARC and p53 has been described, but we found no correlation between p53 expression levels and ARC levels.
  
  
  CONCLUSIONS
  Further studies are needed to define the exact role of ARC in apoptotic signaling and thus its role in chemoresistance and survival of tumor cells.
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany. csaba.toth@med.uni-heidelberg.de.|Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany. csaba.toth@med.uni-heidelberg.de.|Center for Integrated Oncology, CIO Biobank, Cologne, Germany. csaba.toth@med.uni-heidelberg.de.
authors.forename: Csaba
authors.initials: C
authors.lastname: Tóth
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Jeannine
authors.initials: J
authors.lastname: Meinrath
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.|National Cancer Institute, Tissue Bank, Heidelberg, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.affiliation: University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Derix
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Fries
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heikaus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D009124:Muscle Proteins / Q000378:metabolism*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009124:Muscle Proteins; C112246:NOL3 protein, human; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: ARC; Apoptosis; Colorectal cancer; Liver metastasis; MMR proteins; p53