Jackson Claire, Browell David, Gautrey Hannah, Tyson-Capper Alison
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Int J Cell Biol. 2013;2013:973584. doi: 10.1155/2013/973584. Epub 2013 Jul 1.
Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. "Individualised" strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.
人类表皮生长因子受体（HER-2）在20%-30%的乳腺癌中过表达，赋予肿瘤细胞生存和增殖优势，使HER-2成为赫赛汀等药物的理想治疗靶点。对肿瘤生物学的持续研究已鉴定出HER-2的剪接变体，其在肿瘤细胞生物学中具有相反的作用。例如，剪接变体Δ16HER-2（由外显子16跳跃产生）增加癌细胞的转化并与治疗耐药性相关；相反，Herstatin（由内含子8保留产生）和p100（由内含子15保留产生）抑制肿瘤细胞增殖。本综述重点关注HER-2剪接变体在癌细胞中的表达和共存与乳腺癌进展及耐药性相关的潜在临床意义。“个体化”策略目前指导乳腺癌治疗；相应地，HER-2剪接变体可能作为未来的预后和预测因素以及潜在治疗靶点具有重要价值。
