Splicing variant DeltaVII-Ets1 is downregulated in invasive Ets1-expressing breast cancer cells.

Transcription factor Ets1 is expressed in invasive breast cancer cells. In T-cells, the splicing variant DeltaVII-Ets1 is naturally produced along with full length Ets1 (fl-Ets1). Though its function is unknown, the lack of important inhibitory domains predicts a regulatory role of DeltaVII-Ets1 in fl-Ets1-controlled transcription. Examining the expression status of DeltaVII-Ets1 in invasive Ets1-producing MDA-MB-231 breast cancer cells, we found that the DeltaVII-Ets1 protein could only be detected when nuclear proteins from these cells were fractionated by ionic exchange chromatography. When overexpressed, DeltaVII-Ets1 was found to be partially degraded in breast cancer cells, but not in Jurkat T-cells or SK-Mel melanoma cells. In contrast, no proteolytic products resulted from ectopic expression of fl-Ets1 suggesting that breast cancer cells are able to specifically cleave DeltaVII-Ets1. Overexpression of DeltaVII-Ets1 reduced survival of MDA-MB-231 cells, but not of MCF-7 cells. A mutant version of DeltaVII-Ets1, lacking first 129 N-terminal amino acids, had no effect. These data suggest that Ets1-producing invasive breast cancer cells specifically downregulate DeltaVII-Ets1, as it may be able to adversely affect the survival of these cells.