Zhang Yi, Sun Li-guang, Shang Hai, Gao Hong, Yu Hui-ying, Gao Shu-mei, Liu Ning
Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Zhonghua Yi Xue Za Zhi. 2003 Jun 10;83(11):976-80.
To explore the expression of acidic fibroblast growth factor (aFGF) and its receptor FGFR1 in ovarian epithelial cancer and observe the effects of aFGF and TPK inhibitor Genistein on intracellular PKC and ERK activity in ovarian epithelial cancer cells line CAOV3.
The expression levels of aFGF and FGFR1 were evaluated by RT-PCR and western blot in 40 cases of ovarian epithelial cancer. The activity of PKC and ERK in cells induced by different concentration of aFGF and Genistein were detected by incorporation of [gamma-(32)P]-ATP into exogenous substrate.
The expression levels of aFGFmRNA and FGFR1mRNA in the ovarian epithelial cancer were 0.981 +/- 0.130 and 1.047 +/- 0.148, respectively. Compared with normal ovary, ovarian tumor like condition and benign ovary tumors, the difference was significant (P < 0.05). The expression levels in stage III - IV were significantly higher than those in stage I - II (P < 0.05). There were overexpression of aFGF and FGFR1 in the ovarian epithelial cancer in western blot, too. The intracellular PKC and ERK activity increased with aFGF in a dose dependent manner, Genistein suppressed the intracellular PKC and ERK activity also in a dose dependent manner.
aFGF may play an important role in carcinogenesis, development and invasion of ovarian epithelial cancer. Its receptor in human ovarian cancer cell line CAOV3 possessed TPK activity. These tyrosine-specific protein phosphorylation may initiate a cascade of biochemical events, which may increase the intracellular PKC and ERK activity. PKC and ERK locate downstream of TPK in CAOV3 cell line.
探讨酸性成纤维细胞生长因子（aFGF）及其受体FGFR1在卵巢上皮癌中的表达，并观察aFGF及酪氨酸蛋白激酶（TPK）抑制剂金雀异黄素对卵巢上皮癌细胞株CAOV3细胞内蛋白激酶C（PKC）和细胞外信号调节激酶（ERK）活性的影响。
采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测40例卵巢上皮癌组织中aFGF和FGFR1的表达水平。通过[γ-(32)P]-ATP掺入外源性底物的方法，检测不同浓度aFGF和金雀异黄素诱导的细胞中PKC和ERK的活性。
卵巢上皮癌组织中aFGFmRNA和FGFR1mRNA的表达水平分别为0.981±0.130和1.047±0.148。与正常卵巢组织、卵巢瘤样病变及卵巢良性肿瘤相比，差异有统计学意义（P<0.05）。Ⅲ-Ⅳ期卵巢上皮癌组织中aFGF和FGFR1的表达水平明显高于Ⅰ-Ⅱ期（P<0.05）。蛋白质印迹法检测结果显示，卵巢上皮癌组织中aFGF和FGFR1也存在过表达。细胞内PKC和ERK活性随aFGF浓度的增加呈剂量依赖性升高，金雀异黄素也呈剂量依赖性抑制细胞内PKC和ERK活性。
aFGF可能在卵巢上皮癌的发生、发展及侵袭过程中起重要作用。人卵巢癌细胞株CAOV3中的aFGF受体具有TPK活性。这些酪氨酸特异性蛋白磷酸化可能引发一系列生化事件，从而增加细胞内PKC和ERK活性。在CAOV3细胞株中，PKC和ERK位于TPK的下游。
