Altering Ets Activity to Reverse Transformation of Breast Cancer Cells
Abstract
The Ets family transcription factors are downstream targets of most activated signal transduction steps identified in tumor cells. Interfering with Ets-dependent transcription by expression of the Ets2 DNA binding domain (Ets2DBD) can inhibit or reverse Ras-mediated cellular transformation. Thus, altering Ets activity may be an effective way to reverse the effects of aberrant signal transduction pathways in breast cancer. As a model system, we analyzed the effects of stably expressing a variety of Ets2 constructs in Ras-transformed NIH3T3 (DT) cells. Similar to the Ets2DBD, expression of just the Ets2 transactivation domains strongly inhibited DT cell anchorage-independent growth, but unlike the Ets2DBD, did not reverse the transformed cell morphology. Unexpectedly, high expression of full-length Ets2, a transcriptional activator, broadly reversed the transformed properties of DT cells, including anchorage independent growth, transformed morphology, and tumorigenicity, without impairing attached cell growth. Furthermore, increasing full-length Ets2 transcriptional activity by fusing it to the VPl6 transactivation domain enhanced its ability to reverse DT cell transformation. These findings form a strong basis for our current studies examining the effects of either inhibiting or stimulating Ets- dependent transcription on the transformed state of human breast tumor cell lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1999
- Accession Number
- ADA369716
Entities
People
- Gabriele E. Foos
Organizations
- Sanford Burnham Prebys Medical Discovery Institute