1. Immunohistochemical detection of the pro-apoptotic Bax∆2 protein in human tissues.
- Author
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Mañas, Adriana, Yao, Qi, Davis, Aislinn, Basheer, Sana, Beatty, Evan, Zhang, Honghong, Li, Jiajun, Nelson, Adam, Zhang, Huaiyuan, and Xiang, Jialing
- Subjects
CONNECTIVE tissues ,TISSUES ,INVERSE relationships (Mathematics) ,APOPTOSIS ,PROTEINS ,COLON (Anatomy) ,RNA splicing - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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