Incidence of
cancer in the epididymis is very rare. It is proposed that
proteins specific to this organ may contribute to this unique property. We previously demonstrated that
siRNA-mediated knockdown of SPAG11A
mRNA resulted in increased proliferation of epididymal epithelial cells, whereas overexpression of this gene caused reduced proliferation in immortalized cell lines. In this study, we evaluated the
oncogenesis-related anatomical and transcriptome changes in the epididymis of SPAG11A-immunized rats challenged with a low dose of diethyl
nitrosamine (DEN). DEN treatment or SPAG11A immunization alone did not cause any histopathological changes in the epididymis. Interestingly, indications of
oncogenesis were observed in SPAG11A-immunized + DEN-treated rats. Using high throughput sequencing, we observed that 3549 transcripts that were differentially expressed in the caput epididymis of DEN only-treated rats displayed similar differential expression in the caput epididymis of SPAG11A-immunized rats, indicating that the microenvironment that contributes to
oncogenesis sets in when SPAG11A
protein is ablated. Differential expression of genes that are involved in 10 major
cancer related pathways was also analyzed. Majority of the genes related to these pathways that were differentially expressed in the caput epididymis of DEN only-treated rats also showed similar pattern in the caput epididymis of SPAG11A-immunized rats. For the first time, results of our study demonstrate that ablation of SPAG11A by active immunization renders the epididymis susceptible to
oncogenesis and that this
protein may be one of the factors that contributes to the rarity of epididymal
cancer.