Human Dachshund homologue 1 (DACH1) is a key component of the Retinal Determination Gene Network (RDGN), originally identified in Drosophila Melanogaster eye specification. In mammals DACH1 governs morphogenetic processes at early growth stages, cell differentiation and tissue homeostasis. Recent studies demonstrated that aberrant expression of RDGN members is involved in the tumorigenic process of different human cancers. However, the role of DACH1 in cancer onset and progression is still controversial. Four alternatively spliced transcripts encoding different isoforms have been described for human DACH1 gene with different molecular weight (100 kDa, 95 kDa, 75kDa and ~52/57 kDa) (AyresJA, Genomics 2001) even though no studies have been conducted so far on the role of different DACH1 isoforms in human cancers. In our present study, we want to elucidate the role of full-length DACH1 isoform (DACH1FL) in prostate tumorigenic process, the molecular mechanisms underlying its over-expression in prostate carcinoma (PCa) cell line PC3 and its expression level in human PCa samples. We are studying the expression and subcellular distribution of DACH1 in normal and tumor prostate (PCa) tissues by human PCa biopsies with different tumor stages by immunohistochemistry. On the basis of these data, we will analyze these primary tumor and normal samples by western blot to identify the presence of different DACH1 splicing variants. In addition, our aim is to investigate the functional role of DACH1 full-length isoform (DACH1FL) in modulating radioresistance in prostate cancer cell line PC3. The ultimate goal of this project is to define DACH1FL as a prognostic marker in prostate cancer.
