BRCA1 is a tumor-suppressor gene responsible for hereditary breast and ovarian cancers. Characterization of alternately spliced forms of BRCA1 may identify the region of the gene responsible for its function. Here, we cloned and characterized a new BRCA1 splicing variant from the breast cancer cell line ZR-75-30. This transcript, named BRCA1-E1aA-Delta2-17, lacks most exons found in full-length BRCA1, but maintains the original reading frame. We detected expression of the BRCA1-E1aA-Delta2-17 transcript in several human cell lines and tumor tissues, and the fusion protein GFP-BRCA1-E1aA-Delta2-17 localized to the nucleus. Likewise, overexpression of the BRCA1-E1aA-Delta2-17 transcript resulted in cell death as measured by the MTT assay, and fluorescence activated cell sorting (FACS) assays confirmed that this was caused by cellular apoptosis. Our data imply that BRCT domains of the BRCA1 play a role in the cellular apoptosis we observed, and suggest that elucidating the specific function of each of the domains could aid in understanding the exact role of the BRCA1 tumor suppressor.

中文翻译：

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新的BRCA1变体的克隆和表征：BRCT域在凋亡中的作用。

BRCA1是负责遗传性乳腺癌和卵巢癌的肿瘤抑制基因。BRCA1的交替剪接形式的表征可能会确定负责其功能的基因区域。在这里，我们克隆并鉴定了来自乳腺癌细胞系ZR-75-30的新BRCA1剪接变体。该转录本名为BRCA1-E1aA-Delta2-17，缺少全长BRCA1中发现的大多数外显子，但保持原始阅读框架。我们检测到BRCA1-E1aA-Delta2-17转录本在几种人类细胞系和肿瘤组织中的表达，以及融合蛋白GFP-BRCA1-E1aA-Delta2-17定位于细胞核。同样，通过MTT分析测定，BRCA1-E1aA-Delta2-17转录本的过表达导致细胞死亡，荧光激活细胞分选（FACS）分析证实这是由细胞凋亡引起的。