FBI-1 and choriocarcinoma cell proliferation

Abstract

Gestational trophoblastic disease (GTD) includes a spectrum of diseases that involve abnormal growth of trophoblastic cells inside the uterus. It can range from benign hydatidiform moles (HM) to frankly malignant choriocarcinoma, placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumour (ETT). Most choriocarcinoma arise from HM but can develop from any pregnancy related events such as ectopic pregnancy, live-birth or stillbirth. Being the most aggressive neoplasm in GTD, choriocarcinoma can develop widespread metastasis and can be fatal. FBI-1 (Pokemon) is a transcriptional factor that is often overexpressed in various types of human cancer. We have reported overexpression of FBI-1 in ovarian cancer in association with cell proliferation and invasiveness. Our recent study also suggested that overexpression of FBI-1 in HM was related to subsequent development of gestational trophoblastic neoplasia (GTN). In this study, we evaluated the role of FBI-1 gene and choriocarcinoma cell proliferation. By MTT assay, the proliferation rates of two choriocarcinoma cell lines (JAR and JEG-3) was found to decrease when FBI-1 was downregulated by shRNA approach with statistical significance reached in JEG-3 (p < 0.05). By quantitative real time PCR, the relative levels of a panel of stem cell related genes, including Shh, Patched, Gli1, Gli2, Gli3, Kif7, Nanog, Oct4, Sox2, and Stat3, were assessed after knockdown of FBI-1 gene. Significant downregulation of Shh (Sonic Hedgehog) transcript in choriocarcinoma cells in association with reduced proliferation. In conclusion, FBI-1 may play a role in choriocarcinoma cell proliferation and FBI-1 may be explored as one potential therapeutic target for GTD in the future.