Truncated ETV1, fused to novel tissue-specific genes, and full-length ETV1 in prostate cancer
In this study, we describe the properties of novel ETV1 fusion genes, encoding N-truncated ETV1 (dETV1), and of full-length ETV1, overexpressed in clinical prostate cancer. We detected overexpression of novel ETV1 fusion genes or of full-length ETV1 in 10% of prostate cancers. Novel ETV1 fusion partners included FOXP1, an EST (EST14), and an endogenous retroviral repeat sequence (HERVK17). Like TMPRSS2, EST14 and HERVK17 were prostate-specific and androgen-regulated expressed. This unique expression pattern of most ETV1 fusion partners seems an important determinant in prostate cancer development. In transient reporter assays, full-length ETV1 was a strong transactivator, whereas dETV1 was not. However, several of the biological properties of dETV1 and full-length ETV1 were identical. On stable overexpression, both induced migration and invasion of immortalized nontumorigenic PNT2C2 prostate epithelial cells. In contrast to dETV1, full-length ETV1 also induced anchorage- independent growth of these cells. PN T2C2 cells stably transfected with dETV1 or full-length ETV1 expression constructs showed small differences in induced expression of target genes. Many genes involved in tumor invasion/metastasis, including uPA/uPAR and MMPs, were up-regulated in both cell types. Integrin β3 (ITGB3) was clearly up-regulated by full-length ETV1 but much less by dETV1. Based on the present data and on previous findings, a novel concept of the role of dETV1 and of full-length ETV1 overexpression in prostate cancer is proposed.
|Keywords||beta3 integrin, immediate early protein BZLF1, transcription factor, transcription factor ER81, transcription factor foxp1, unclassified drug|
|Persistent URL||dx.doi.org/10.1158/0008-5472.CAN-07-5930, hdl.handle.net/1765/14456|
Hermans, K.G.L., van der Korput, H.A.G.M., van Marion, R., van de Wijngaart, D.J., van der Made, A.Z., Dits, N.F., … Trapman, J.. (2008). Truncated ETV1, fused to novel tissue-specific genes, and full-length ETV1 in prostate cancer. Cancer Research, 68(18), 7541–7549. doi:10.1158/0008-5472.CAN-07-5930