The C-terminal common to group 3 POTES (CtG3P): a newly discovered nucleolar marker associated with malignant progression and metastasis.

A gene family expressed in prostate, ovary, testis and placenta (POTEs) is newly defined and primate-specific. POTE genes have 13 paralogs, which are dispersed in 8 chromosomes and divided into three groups. The proteins encoded by these genes contain three domains: An N-terminal, ankyrin repeats and a C-terminus. Previous studies suggest that POTE proteins are localized in the inner aspect of cellular membrane and are considered as cancer-testis antigens, because they expressed widely in cancers, but in limited benign tissues. In this study, we will study the subcellular distribution of all POTE proteins and their associations with the progress and metastasis of malignancies. By performing Immunohistochemistry, Immunocytochemistry and immunofluorescence assay on tissue microarray slides containing tissues with different pathology and origins or on cell lines, we found that the epitopes of N- and C-terminals of all detected POTEs were widely expressed in benign and malignant tissues. Among these epitopes, C-terminal common to group 3 POTEs (CtG3P) was the only portion localized in nucleoli. The nucleolar IHC scores for CtG3P was lowest in benign tissues (4.47 ± 3.43), significantly higher in localized malignancies (5.32 ± 3.36, p = 3.63E-02), and highest in metastatic malignancies (7.90 ± 2.29, p = 8.13E-12). The CtG3P was better in differentiation of benign from malignant changes, and/or in differentiation of localized from metastatic cancers as compared with Ki-67 and AgNORs. In addition, transient transfection of siRNA against mRNA of group 3 POTEs influences the growth and survival of MCF-7 cells in vitro in a dose dependent manner.