Effect and possible mechanism of fibroblast growth factor 9 on cell proliferation in mouse Leydig cell lines

  • 杜 姿慧

Student thesis: Master's Thesis


Fibroblast growth factors (FGFs) interacts with its receptor fibroblast growth factor receptor (FGFR) to control a wide range of biological functions such as cell proliferation anti-apoptosis migration and differentiation Previous studies have shown that fibroblast growth factors 9 (FGF9) has an important role in embryo development and FGF9 protein level is low and the expression of FGF9 is restricted in few adult organs FGF9 is found to be involved in sex-determination In our lab we have demonstrated that FGF9 stimulated steroidogenesis in mouse Leydig cells through MAPK PI3K and PKA signal transduction pathways On the other hand studies have reported that abnormal expression of FGF9 usually results in colon ovarian and prostate cancers in human Also study indicated that FGF9 could increase proliferation rate and cell mobility in ovarian cancer These phenomena illustrated that over-expression of FGF9 could contribute to the cancer occurrence Here we sought to investigate the roles of FGF9 on mouse Leydig normal and tumor cell line The results showed that FGF9 could increase cell viability in TM3 with an increased trend in MA-10 The proliferation related marker proteins PCNA and Ki67 were significantly increased after FGF9 treatment in TM3 not in MA-10 However we found that FGF9 could increase EDU positive cell in these cell lines In mechanistic study AKT/mTOR pathway was not activated upon FGF9 treatment in both of cell lines whereas FGF9 could active phosphor-JNK and -ERK1/2 in TM3 and phosphor-ERK1/2 in MA-10 FGF9 could also activate the expression of PLCγ1 in TM3 cells but not in MA-10 cells PI staining study further detected the effect of FGF9 on cell cycle regulation We found that FGF9 promoted cell cycle progression in TM3 but not in MA-10 cells The cell cycle related proteins CDK1 CDK2 CDK4 cyclin A cyclin B cyclin D1 were increased in TM3 but not in MA-10 Besides the cell cycle inhinitory proteins p27 was decreased in TM3 but not in MA-10 In addition FGF9 significantly increased cell migration in TM3 after 3 9 and 12 hr and MA-10 after 48 hr treatments respectively in wound-healing assay Also the transwell assay showed that both migration and invasion were increased in both TM3 and MA-10 cell lines In conclusion FGF9 induces cell proliferation on TM3 cells through the activation of signal transduction and speed up cell cycle progression whereas FGF9 only activates ERK to have a minor effect on cell proliferation in MA-10 cells Besides FGF9 could enhance on cell migration and invasion in TM3 and MA-10 cells
Date of Award2015 Jul 13
Original languageEnglish
SupervisorBu-Miin Huang (Supervisor)

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