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Background Estrogen plays an important role in the progression of ovarian cancer in humans. FOXP1 belongs to the forkhead/winged-helix transcription factor family, and previous research indicated that FOXP1 functioned as a tumor suppressor gene. FOXP1 may be similar to FOXA1 and is closely related to steroid hormone receptors, but the relationship between FOXP1 and ER currently remains unclear. Methods Ovarian tumors (60 malignant cases, 26 borderline cases, and 13 benign cases) and 14 normal ovarian tissues were collected retrospectively. Immunohistochemistry, western blotting and real-time PCR were used to characterize the expression patterns of FOXP1, ERα, and ERβ both at the mRNA and protein levels. We also used co-immunoprecipitation and immunofluorescent colocalization to investigate whether a correlation exists between FOXP1 and ERα/ERβ in ovarian cancer tissues. Results The mRNA level for FOXP1 and ERβ in ovarian carcinoma tissues decreased, while the expression level of ERα mRNA increased compared with normal ovarian tissues. With an increase in the degree of ovarian carcinoma malignancy, the ERα expression level also increased. The expression pattern of ERβ in ovarian neoplasms was similar to that of the FOXP1 protein; presenting nuclear staining decreased, while cytoplasmic expression increased. Colocalization of FOXP1, ERα, and ERβ was present in the cytoplasm, with ERβ specific co-localization with FOXP1 in the perinuclear area. While immunoprecipitates created with FOXP1 mouse anti-human monoclonal antibody showed a positive reaction to an anti-ER antibody, immunoprecipitates containing anti-ER antibody and react to anti-FOXP1 antibody. Conclusion Interactions between FOXP1 and ER may play a pivotal role in the progression of ovarian cancer, and the activation or induction of FOXP1 and ERβ expression in cancer cells may inhibit tumor proliferation. [ABSTRACT FROM AUTHOR]

To study Human epididymis protein 4 (HE4) surface fucosylation and to determine the effects and significance of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, we investigated four types of ovarian cancer cells and found that six fucosylated antigens (Lewis y, Lewis x, Lewis a, Lewis b, sLewis a, and sLewis x) were identified on HE4 in ovarian cancer cells. Moreover, modification of the type II sugar chain (Lewis y, Lewis x, and sLewis x) was significantly higher than the type I sugar chain (Lewis a, Lewis b, sLewis a) of the lactose series. To confirm the effects of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, the CaoV-3 cells with high Lewis y antigen on the HE4 surface and ES-2 cells, with high Lewis x antigen but low Lewis y antigen, were investigated. We found that the expression levels of HE4 and Lewis y increased in both cell lines while the level of Lewis x didn't have any change after transfection. Furthermore, the high expression of Lewis y antigen significantly enhanced the HE4-mediated invasion and metastasis of ovarian cancer cells. The invasion and metastasis capacities were significantly decreased after Lewis y antibody blocking. This study demonstrates that overexpression of the Lewis y antigen on HE4 promotes ovarian cancer cell invasion and metastasis, which is likely to be used as a target for the clinical treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown. Here, we identify an AP-1 binding site in FUT1 promoter in ovarian cancer cells. c-Jun promotes FUT1 expression, thereby enhancing Lewis y biosynthesis in various ovarian cancer cell lines. Moreover, EMSA, luciferase activity and ChIP assays demonstrate c-Jun directly interacts with FUT1 promoter. Furthermore, FUT1 mediates c-Jun-induced cell proliferation in ovarian cancer cells. In human ovarian cancer samples, c-Jun overexpression is linked to malignant degree and positively correlated to FUT1 and Lewis y expression. Taken together, c-Jun could transcriptionally modulate FUT1 expression in ovarian cancer, implicating the potential application of c-Jun inhibitors for human ovarian cancer therapy. [ABSTRACT FROM AUTHOR]