The expression and significance of pThr32-FOXO3a in human ovarian cancer.

FOXO3a possesses a large series function, including cellular proliferation, transformation, differentiation, and longevity. Recent studies suggested that the different localization of FOXO3a in nucleus and cytoplasm has different functions. And phosphorylation of FOXO3a at threonine-32 plays an important role in deciding FOXO3a localization. In this study, we investigated the role of pThr32-FOXO3a and Ki-67 in human ovarian cancer. Furthermore, we study the effect of mutant of FOXO3a (T32A) on the ovarian cancer cells. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 46 specimens. And in vitro, we detect the contribution of wild-type and mutant FOXO3a on the ovarian cancer cell proliferation. We found that the pThr32-FOXO3a was overexpressed in human ovarian cancer, and pThr32-FOXO3a expression correlated significantly with lymph node involvement (P = 0.015). And the proliferation index Ki-67 was significantly associated with lymph node involvement (P = 0.000) and disease stage (P = 0.003). Kaplan-Meier analysis revealed that survival curves of low versus high expressers of pThr32-FOXO3a and Ki-67 showed a highly significant separation in human ovarian cancer (P < 0.01). Transfection of FOXO3a (T32A) resulted in a significant increase in cells in G(1) phase than transfection of wild-type FOXO3a and control cells. Our results suggested that pThr32-FOXO3a and Ki-67 expression may be considered to be important prognosis in human ovarian cancer. In vitro studies suggested that FOXO3a (T32A) was a more powerful cell cycle inhibitor, although both the wild type and mutant forms of FOXO3a were effective.