Introduction & Objectives
Prostate cancer (PC) is the most common malignancy in the male population however; molecular diagnostic/prognostic markers that better define this pathology are very limited and frequently found to be unspecific (i.e. PSA). Therefore, it is necessary to provide new clues for novel diagnostic/prognostic/therapeutic targets in this pathology. Some Genes belong to a family of homeodomain-containing transcription factors that determine cell/tissue identity during normal embryonic development which, have been shown to be re-expressed by different tumoral cell-types. Interestingly, some studies have indicated that the engrailed variants (EN1 and EN2) might be used as a potential diagnostic markers of early PC however; these few studies are conflicting and incomplete and, to date, limited information is available concerning the presence of these variants in PC-cells. Therefore, the main goals of this study were to analyse the expression levels of EN1- and EN2-variants in PC-tissues and cell lines and, to determine urinary levels of EN2-variant in patients with and without PC.
Material & Methods
To that end, we implemented a triple strategy by using: 1) paraffin-embedded PC-tissues obtained from radical prostatectomies and its adjacent normal-control tissues; 2) normal and androgen-dependent (LnCaP/VCaP/22Rv1) and androgen-independent (DU145/PC3) PC-cell lines and; 3) Urinary fluids from patients with PC and control-patients.
Expression of EN2-variant, but not EN1-variant, was up-regulated in PC-tissues compared to normal-adjacent tissues (p<0.05). Moreover, EN1/EN2-variants were not expressed in a normal-prostate cell-line while, EN2-variant was over-expressed in all PC cells-lines analyzed (LnCaP>>DU145>VCaP>PC3>22Rv1). Interestingly, only DU145 cells expressed EN1-variant. Median urinary levels of EN2-variant collected from PC and controls-patients without prostate massage were similar (~0.8ng/ml).
Altogether, our ongoing studies suggest a potential role of EN-variants, especially EN2, in PC cells. Therefore, additional experiments are planned to determine the functional role of these EN-variants in PC-cells as wells as, additional measures of urinary and plasma EN2 levels in PC and control patients following a prostate massage.
Funding: PI13-00651, PI-0639-2012, BIO-0139, CTS-1406, BFU2013-43282-R, CD11/00276 and CIBERobn
Keywords: Prostate Cancer, Engrailed-1 y -2 variants, diagnostic/therapeutic markers