Differential expression of ETS family members in prostate cancer tissues and androgen-sensitive and insensitive prostate cancer cell lines

Abstract

The ETS family of transcription factors plays important roles in both normal and neoplastic cells for different biological processes such as proliferation, differentiation, development, transformation, apoptosis, migration, invasion and angiogenesis. The 27 ETS factors are probably a part of complex regulatory networks including interactions among family members. In human prostate cancer, rearrangements have been found in several genes of the ETS family resulting in chimeric oncoproteins. In a previous study we found that the ETS family prototype, Ets-1 affects biological properties of PC3 prostate cancer cells. In a first effort to understand the cooperative interactions between different ETS factors in prostate cancer, in the present study we examined the expression pattern of all 27 ETS members using quantitative RT-PCR (qRT-PCR) in the androgen-sensitive VCaP and LNCaP, and the androgen-insensitive PC3 and DU-145 prostate cancer cell lines as well as in human prostate cancer tissue samples. We further investigated whether the ETS family prototype, Ets-1, regulates other ETS family members by examining the effect of Ets-1 blockade in PC3 cells on their expression. We found an expression specificity of various ETS family members in the prostate cancer cell lines which might reflect their different biological properties. In human prostate samples only 3 among the 27 ETS family members (Ehf, Elk-4 and Ets-2) showed significant expression differences between normal and cancerous prostate glands. We finally demonstrate that the family prototype, Ets-1, regulates the family members Elf-1, Elf-2, Elk-1, Etv-5 and Spi-1 in PC3 prostate cancer cells. Chimeric oncoproteins containing ETS family members arising due to frequent translocations in prostate cancer are probably part of a regulatory network involving other ETS family members as well.