FBI-1 and choriocarcinoma cell proliferation

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).GTD are considered curable if the patient is correctly diagnosed and receive appropriate treatment during the early stage of the disease. About 15% -30% of hydatidiform moles will develop persistent GTD, but majority of them can usually resolved by surgical intervention and post-operation weekly serial serum β-hCG level monitoring. In contrast, choriocarcinoma is a frankly malignant gestational trophoblastic neoplasm (GTN). 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 transcription 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 neoplasms(GTN). In this study, we evaluated the role of FBI-1 inchoriocarcinoma 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 hedgehog pathway related genes, including SHH, SMO, GLI1, GLI2, GLI3, and KIF7 were assessed after knockdown of FBI-1 gene. Sonic hedgehog (SHH) was found to be consistently downregulated in JEG-3 and JAR transfected with FBI-1 shRNA constructs. In conclusion, FBI-1 may play a role in choriocarcinoma cell proliferation and FBI-1 may be explored as a potential therapeutic target for GTD in the future.published_or_final_versionPathologyMasterMaster of Medical Science