Hsiu-Mei Chen

Fibroblast Growth Factor-9 Is an Endometrial Stromal Growth Factor

Fibroblast growth factor-9 (FGF-9) is an autocrine/paracrine growth factor considered to be important for the growth and survival of motorneurons and prostate. In this study, we found that FGF-9 was expressed at high levels in normal uterine endometrium, especially during the late proliferative phase, which is coincident with the rise of estradiol and the time of uterine endometrial proliferation. Using quantitative RT-PCR analysis, we found that FGF-9 mRNA was expressed primarily by endometrial stromal cells. High affinity receptors of FGF-9 were detected in both epithelial and stromal cells but with distinct patterns. FGFR2IIIc and FGFR3IIIc are abundant in endometrial stromal cell. FGFR2IIIb is mostly expressed in endometrial epithelial cells, whereas FGFR3IIIb is found in both epithelial and stromal cells. Treatment with FGF-9 induces endometrial stromal proliferation in a dose-dependent manner. Expression of FGF-9 in stromal cells was induced by 17β-estradiol but not by progesterone. Furthermore, the...

Production and characterisation of a monoclonal antibody (Cx-99) against cervical carcinoma.

An IgG1 monoclonal antibody (MAb Cx-99) has been established which recognises a surface antigen on epithelial cells, but not on fibroblastic or hematopoietic cells. Immunohistochemical studies showed that this antigen was present in all 37 squamous cell carcinomas (SCC) including 33 cervical SCC, and 30 of the 32 adenocarcinomas examined; most of the 33 cervical SCC were stained extensively. It was also detected in the culture medium of cervical cancer cell lines. In the normal cervix, this antigen was restricted to the undifferentiated basal cells. This observation suggests that the widespread expression of the antigen was triggered by oncogenesis. The MAb Cx-99 recognised an epitope on an asialyted glycoprotein which has an apparent molecular weight of 37 kilodaltons (kD) (and 2 minor proteins at 18 and 27 kD) and an isoelectric point (pI) of 5.3. It may have potential for studies on differentiation and oncogenesis and for diagnostic applications.

Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen

Fibroblast growth factor-9 (FGF-9) is a steroid-regulated mitogen and survival factor for nerve and mesenchymal cells. In the current study, we determined the expression pattern and functional roles of FGF-9 in the ectopic endometriotic lesions. We found that FGF-9 and its receptors were effectively expressed by ectopic endometriotic tissues. The expression of FGF-9 was greater in the early stage of endometriosis, compared with the severe stage, which is consistent with concentration of 17 beta-estradiol in the peritoneal fluid of women with endometriosis. In addition, expression of FGF-9 in ectopic endometriotic stromal cell was inhibited by treatment with ICI 182,870 indicating it is likely regulated by estrogen in an autocrine manner. Administration of 17 beta-estradiol induced FGF-9, FGF receptor 2IIIc, and FGF receptor 3IIIc expression in endometriotic stromal cells. Concordant with this result, treatment of endometriotic stromal cells with 4-hydroxyandrostenedione (an aromatase inhibitor) or ICI 182,870 inhibited their proliferation, and that was reversed by coadministration with 17 beta-estradiol or FGF-9. In conclusion, expression of FGF-9 in endometriotic stromal cells is associated with aberrant production of estrogen. The capability of proliferation possessed by endometriotic stromal cell during menstruation when ovarian 17 beta-estradiol is in the nadir may be mediated, at least in part, by autocrined estrogen-stimulated expression of FGF-9 and its receptors.

Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington’s Disease

Background/Aims: Huntington’s disease (HD) is a heritable neurodegenerative disorder, and there is no cure for HD to date. A type of fibroblast growth factor (FGF), FGF9, has been reported to play prosurvival roles in other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. However, the effects of FGF9 on HD is still unknown. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD. Methods: In this study, STHdhQ7/Q7 (WT) and STHdhQ111/Q111 (HD) striatal knock-in cell lines were used to evaluate the neuroprotective effects of FGF9. Cell proliferation, cell death and neuroprotective markers were determined via the MTT assay, propidium iodide staining and Western blotting, respectively. The signaling pathways regulated by FGF9 were demonstrated using Western blotting. Additionally, HD transgenic mouse models were used to further confirm the neuroprotective effects of FGF9 via ELISA, Western blotting and immunostaining. Results: Results show that FGF9 not only enhances cell proliferation, but also alleviates cell death as cells under starvation stress. In addition, FGF9 significantly upregulates glial cell line-derived neurotrophic factor (GDNF) and an anti-apoptotic marker, Bcl-xL, and decreases the expression level of an apoptotic marker, cleaved caspase 3. Furthermore, FGF9 functions through ERK, AKT and JNK pathways. Especially, ERK pathway plays a critical role to influence the effects of FGF9 toward cell survival and GDNF production. Conclusions: These results not only show the neuroprotective effects of FGF9, but also clarify the critical mechanisms in HD cells, further providing an insight for the therapeutic potential of FGF9 in HD.