International Journal of Colorectal Disease

, Volume 19, Issue 6, pp 538–544

BAX and caspase-5 frameshift mutations and spontaneous apoptosis in colorectal cancer with microsatellite instability

  • Joerg Trojan
  • Angela Brieger
  • Jochen Raedle
  • Nicole Weber
  • Susanne Kriener
  • Bernd Kronenberger
  • Wolfgang F. Caspary
  • Stefan Zeuzem
Original Article

DOI: 10.1007/s00384-004-0597-1

Cite this article as:
Trojan, J., Brieger, A., Raedle, J. et al. Int J Colorectal Dis (2004) 19: 538. doi:10.1007/s00384-004-0597-1

Abstract

Background and aims

Hereditary nonpolyposis colorectal cancer (HNPCC) and a subset of sporadic colorectal cancers are characterized by microsatellite instability (MSI) and inactivating frameshift mutations of target genes. Inactivation of BAX, caspase-5 (cas-5), and other genes coding for pro-apoptotic proteins might contribute to tumor progression by enhancing escape from apoptosis. The aim of this study was to further characterize the role of BAX and cas-5 inactivation for spontaneous apoptosis.

Methods

Twenty-five colorectal cancers with MSI were analyzed for frameshift mutations in the BAX (G)8 and cas-5 (A)10 tract by fluorescence PCR, cloning, and sequencing. The rate of spontaneous apoptosis was examined by in situ DNA nick end-labeling. The results were compared with 25 stage-matched microsatellite stable (MSS) colorectal cancers.

Results

In colorectal cancer with MSI frameshift mutations in BAX and cas-5 were present in 16 of 25 (64%) and in 12 of 25 (48%) tumors, respectively, whereas neither mutant BAX nor cas-5 alleles were detected in all stage-matched sporadic MSS colorectal cancer. Tumors with MSI showed a higher apoptotic rate than MSS tumors (2.5±1.0 vs. 2.1±0.7; p <0.05), whereas the presence of BAX or cas-5 frameshift mutations had only minor influence on this finding (2.4±1.1% and 2.5±0.9%, respectively).

Conclusion

Mismatch-repair deficiency itself is associated with increased spontaneous apoptosis, not further accelerated by either inactivating BAX or cas-5 frameshift mutations.

Keywords

ApoptosisColorectal cancerMicrosatellite instabilityTumorigenesis

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Joerg Trojan
    • 1
  • Angela Brieger
    • 1
  • Jochen Raedle
    • 2
  • Nicole Weber
    • 1
  • Susanne Kriener
    • 1
  • Bernd Kronenberger
    • 2
  • Wolfgang F. Caspary
    • 1
  • Stefan Zeuzem
    • 2
  1. 1.2nd Department of Medicine and Senckenberg Center of PathologyJohann Wolfgang Goethe University Medical CenterFrankfurt a.M.Germany
  2. 2.2nd Department of Internal MedicineUniversity HospitalHomburg/SaarGermany