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The Human Epididymis Protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer
(EOC). We previously ascertained the serum HE4 level was signifi cantly elevated in the
majority of all ovarian cancers but not in benign diseases or health control, therefore, it is useful
for application in clinical diagnosis, even for the malignant ovarian carcinoma patients at early
stage. Although the molecular mechanism of the HE4 protein is unknown, the HE4 (WFDC2)
gene is amplifi ed at high levels in ovarian cancers. We therefore performed experiments to
explore preliminary the functions of HE4 in ovarian cancer cells. Here, we reported that HE4
was specially overexpressed in human ovarian cancer SKOV3 cells. And, we showed that HE4
secreted by ovarian cancer cells enhances cell adhesion and motility. At the molecular level, HE4
promotes epidermal growth factor receptor activation, increases the expression of cell adhesion
molecules on the cell surface. Moreover, stable transfection of cells with plasmid expressing
HE4-pcDNA3.1 promoted cell migration and adhesion. Correspondingly, HE4 enhanced
migration of cells was also inhibited by HE4-shDNA expression. Interestingly, following
down-regulation of HE4, the phosphorylations of JNK and ERK were dramatically decreased.
Th is study suggested that expression of HE4 was associated with cancer cell proliferation and
migration through MAPK signaling pathway. Taken together, our results provide the fi rst
evidence of the cellular and molecular mechanisms that may underlie the motility-promoting
role of HE4 in EOC. In addition, these results underscore the important functional implications
of HE4 processing in ovarian cancer progression. Th erefore, it might be taken into consideration
in future studies that examine the role of HE4 as a target for gene-based therapy.
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