Abstract 1083: Expression of an estrogen-regulated variant transcript of the peroxisomal branched chain fatty acid oxidase, ACOX2, in breast cancer

Abstract Alternate transcripts from a single gene locus greatly enhance the combinatorial flexibility of the human transcriptome. Different patterns of exon usage have been observed when comparing normal tissue to cancers, suggesting that variant transcripts may play a role in the tumor phenotype. In this study we show that an intronic start variant of ACOX2, peroxisomal Acyl-CoA oxidase 2 (ACOX2-i9), is expressed and translated into a 25kDa protein in HepG2 cells as well as in several breast cancer cell lines, where it is required for optimal cell proliferation. shRNA knock down of the ACOX2-i9 variant results in decreased cell viability as assessed by colony formation assay of T47D and MDA-MB 436 cells. Moreover, expression of ACOX2-i9 is estrogen regulated, being induced by estradiol and inhibited by tamoxifen in ER+ T47D and Mcf-7 cells, but not in the ER- MDA-MB 436 cell line. This variant transcript is present predominantly in breast tumors as assessed in our initial set of 53 breast cancers and further validated in 87 tumor/normal pairs from the TCGA Breast Cancer dataset. It is specifically enriched in ER+ breast cancers where it's expression is associated with improved outcome. These data identify variant ACOX2 as a potential novel therapeutic biomarker in ER+ breast cancer. Citation Format: Sunniva Bjørklund, Vessela N. Kristensen, Michael Seiler, Grethe I. Grenaker Alnaes, Yao Ming, John Kerrigan, Bjørn Naume, Ravi Sachidanandam, Gyan Bhanot, Anne-Lise Børresen-Dale, Shridar Ganesan. Expression of an estrogen-regulated variant transcript of the peroxisomal branched chain fatty acid oxidase, ACOX2, in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1083. doi:10.1158/1538-7445.AM2015-1083