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

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 Bax?, 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 Bax?2-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 Bax? 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.

SUBMITTER: Manas A 

PROVIDER: S-EPMC7351616 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature