c-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling

c-Rel 通过 PI3K/AKT 信号促进绒毛膜癌细胞的侵袭

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作者:Yoko Sekiya, Eiko Yamamoto, Kaoru Niimi, Kimihiro Nishino, Kenichi Nakamura, Tomomi Kotani, Hiroaki Kajiyama, Kiyosumi Shibata, Fumitaka Kikkawa

Conclusion

These findings suggest that c-Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signaling.

Methods

We examined the expression of NF-κB family proteins in normal placenta and hydatidiform mole tissues as well as extravillous trophoblast (EVT) and choriocarcinoma cell lines by Western blot and immunohistochemistry. Immunoprecipitation was performed to determine which proteins can bind with c-Rel in choriocarcinoma cells. To investigate the roles of c-Rel in choriocarcinoma, we examined the effects of c-Rel knockdown and overexpression on cell proliferation, migration, and invasion using small interfering RNAs and gene activation plasmid.

Objective

Choriocarcinoma is the most common epithelial cancer among gestational trophoblastic diseases (GTDs); the mechanism of trophoblastic carcinogenesis is unknown. This study aimed to examine the expression of NF-κB family proteins in GTDs and placental tissues as well as the roles of c-Rel in choriocarcinoma.

Results

The expression of c-Rel was strong in choriocarcinoma and EVTs, but very weak in villi of normal placenta and hydatidiform mole. Immunoprecipitation suggested that c-Rel heterodimerizes with p65 in choriocarcinoma. c-Rel knockdown reduced invasion, migration, and AKT phosphorylation in choriocarcinoma cells. c-Rel overexpression in choriocarcinoma increased migratory and invasive abilities, and the effect on invasion was inhibited by a PI3K inhibitor.

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