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STAT3 mRNA and protein expression in colorectal cancer: effects on STAT3-inducible targets linked to cell survival and proliferation
  1. Silke Lassmann1,*,
  2. Ingrid Schuster1,*,
  3. Axel Walch2,
  4. Heike Göbel1,
  5. Uta Jütting3,
  6. Frank Makowiec4,
  7. Ulrich Hopt4,
  8. Martin Werner1
  1. 1Institut für Parthologie, Universitätsklinikum Freiburg, Freiburg, Germany
  2. 2Institut für Pathologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany
  3. 3Institut für Biomathematik und Biometrie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany
  4. 4Chirugische Klinik, Universitätsklinikum Freiburg, Freiburg, Germany
  1. Correspondence to:
 Dr S Lassmann
 Institut für Parthologie, Universitätsklinikum 19106 Freiburg, Breisacherstrasse 115a, Germany; silke.lassmann{at}uniklinik-freiburg.de

Abstract

Aims: To evaluate mRNA and protein expression of signal transducers and activators of transcription (STAT)3 in colorectal carcinomas (CRCs) and to define the association of STAT3 activity with the STAT3-inducible targets cyclin D1, survivin, Bcl-xl and Mcl-1.

Materials and methods: Matching serial sections of normal colonic epithelium and invasive CRCs (n = 32) were subjected to quantitative reverse transcriptase polymerase chain reaction specific to STAT3, cyclin D1, survivin, Bcl-xl and Mcl-1, as well as immunohistochemistry. For STAT3 immunohistochemistry, two antibodies, recognising unphosphorylated (UP-) and phosphorylated (tyr705, P-) STAT3 were used. Ki-67 (MIB-1) staining was included as a proliferation marker.

Results: Compared with normal colonic epithelium, UP-STAT3 and P-STAT3 (p = 0.023 and 0.006) protein expression and expression of its associated targets cyclin D1, survivin and Bcl-xl were significantly (all p<0.001) increased in carcinoma. In carcinomas, STAT3 (p = 0.019) and Bcl-xl (p = 0.001) mRNAs were correlated with lymph node status. Moreover, nuclear P-STAT3 protein expression (active state) was associated with the expression of its target genes Bcl-xl (p = 0.038) and survivin (p = 0.01) as well as with Ki-67 (p = 0.017). By contrast, cytoplasmic UP-STAT was significantly linked to Bcl-xl mRNA (p = 0.024) and protein (p = 0.001) as well as to cytoplasmic survivin protein expression (p = 0.019).

Conclusion: Both inactive (UP-STAT3) and active (P-STAT3) STAT3 proteins are markedly increased in invasive CRCs. This is associated with Bcl-xl and survivin induction, increased proliferation and lymph node metastasis. This study therefore provides the basis for further examination of the prognostic or predictive value of these molecular markers in CRC.

  • CRC, colorectal carcinoma
  • QRT-PCR, quantitative reverse transcriptase polymerase chain reaction
  • STAT, signal transducers and activators of transcription

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Footnotes

  • * These authors contributed equally to the work.

  • Competing interests: None declared.

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