Novel identification of the ETS-1 splice variants p42 and p27 in prostate cancer cell lines.

ETS-1 is involved in cellular functions such as proliferation, migration, invasion, apoptosis and angiogenesis. The ETS-1 gene encodes three distinct proteins, ETS-1 p51 encoded by a full-length mRNA, ETS-1 p42 and ETS-1 p27 encoded by an alternatively spliced mRNA lacking exon VII and exons III-VI, respectively. ETS-1 p51, commonly considered to be the active form, has been studied in prostate cancer (PCa). However, the ETS-1 p42 and p27 variants have not yet been identified in PCa. Therefore, we aimed in this study at investigating whether the splice variants p42 and p27 are expressed in the androgen-dependent VCaP and LNCaP and the androgen-independent PC3 and DU-145 PCa cell lines. Using RT-PCR, we found the expression of both splice variants p42 and p27 at the mRNA level in the VCaP, LNCaP, PC3 and DU-145 PCa cell lines. We then confirmed the expression of ETS-1 p51 and its splice variants p42 and p27 at the protein level using an anti-ETS-1 antibody directed against the DNA-binding domain (DBD) in lysates prepared from the latter-mentioned cell lines, as well as in PC3 cell nuclear extract. Moreover, differences in the expression ratios of the ETS-1 splice variants within each cell line were also found. In conclusion, we have demonstrated for the first time the novel identification of the ETS-1 splice variants p42 and p27 in PCa cell lines. It is very likely that the role of ETS-1 p51 in PCa is significantly influenced by the presence of its splice variants ETS-1 p42 and p27 as competition, abundance, affinity, interactions and cross-talk among them will eventually determine the genes that will be targeted and subsequently affect cellular functions. Follow-up studies will need to address in functional terms, the roles of these splice variants in PCa cell lines, as well as their expression in PCa tissues and its correlation with clinical outcome.