Gene expression changes upon knockdown or over-expression of the ETS gene ETV4 in prostate cancer cell lines. Homo sapiens

Chromosomal abnormalities that give rise to elevated expression levels of the ETS genes ETV1, ETV4, ETV5, or ERG are prevalent in prostate cancer, but the function of these transcription factors in carcinogenesis is not clear. Previous work implicates ERG, ETV1, and ETV5 as regulators of invasive growth but not transformation in cell lines. Here we show that the PC3 prostate cancer cell line provides a model system to study the over-expression of ETV4. Anchorage independent growth assays and microarray analysis indicate that high ETV4 expression is critical for the transformation phenotype of PC3 cells. However, genes up-regulated upon ETV4 over-expression were very similar to genes up-regulated by ETV1 over-expression in the RWPE-1 normal prostate cell line. Together these data indicate that the ETV4 dependent transformation phenotype observed in PC3 cells is due to the genetic background of the cell line, rather than a distinct characteristic of ETV4. Furthermore, these findings suggest that the function of ETS genes in prostate cancer may differ based on other genetic alterations in a tumor. Overall design: Two sets of two color experiments. First is PC3 cells expressing one of two independent ETV4 shRNAs versus PC3 cells expressing a control shRNA (luciferase). Second is RWPE-1 cells expressing 3xFlag tagged ETV4 versus RWPE-1 cells with a control (empty) vector.