Immunohistochemical detection of the pro-apoptotic Bax∆2 protein in human tissues

Research output: Contribution to journalArticle

Abstract

The pro-apoptotic Bax isoform Bax∆2 was originally discovered in cancer patients with a microsatellite guanine deletion (G8 to G7). This deletion leads to an early stop codon; however, when combined with the alternative splicing of exon 2, the reading frame is restored allowing production of a full-length protein (Bax∆2). Unlike the parental Baxα, Bax∆2 triggers apoptosis through a non-mitochondrial pathway and the expression in human tissues was unknown. Here, we analyzed over 1000 tissue microarray samples from 13 different organs using immunohistochemistry. Bax∆2-positive cells were detected in all examined organs at low rates (1-5%) and mainly scattered throughout the connective tissues. Surprisingly, over 70% of normal colon samples scored high for BaxΔ2-positive staining. Only 7% of malignant colon samples scored high, with most high-grade tumors being negative. A similar pattern was observed in most organs examined. We also showed that both Baxα and Bax∆2 can co-exist in the same cells. Genotyping showed that the majority of Bax∆2-positive normal tissues contain no G7 mutation, but an unexpected high rate of G9 was observed. Although the underlying mechanism remains to be explored, the inverse correlation of Bax∆2 expression with tissue malignancy suggests that it may have a clinical implication in cancer development and treatment.

Details

Authors
  • Adriana Mañas
  • Qi Yao
  • Aislinn Davis
  • Sana Basheer
  • Evan Beatty
  • Honghong Zhang
  • Jiajun Li
  • Adam Nelson
  • Huaiyuan Zhang
  • Jialing Xiang
External organisations
  • Illinois Institute of Technology
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
JournalHistochemistry and Cell Biology
Publication statusE-pub ahead of print - 2020 Mar 21
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes