CLONING AND FUNCTIONAL IDENTIFICATION OF TWO NOVEL <i>BRCA1 </i>SPLICING VARIANTS
In this investigation, two novel <i>BRCA1 </i>splicing variants were cloned from breast cancer cell line ZR-75-30. These transcripts, named <i>BRCA1</i>-PI21-∆2-21 and <i>BRCA1</i>-∆2-14, lacked most exons of the full length <i>BRCA1 </i>gene but maintained the original reading frame. We also demonstrated the presence of <i>BRCA1</i>-PI21-∆2-21 in several human cell lines. Expression of both variants fused with GFP showed that they targeted different subcellular compartments in the transfected cells. Viability of the cells expressing both fusion proteins decreased notably compared with the viability of cells expressing only GFP. FACS assay confirmed that the overexpression of two splicing variants resulted in cell apoptosis. Taken together, the different subcellular localization and cell effects of two <i>BRCA1 </i>splicing variants imply that they can have different biological functions in breast cancer cells. Elucidating the functions of <i>BRCA1 </i>splice variants would help to understand the exact roles of the <i>BRCA1 </i>gene in tumor suppression.