Valve E, Martikainen P, Seppänen J, Oksjoki S, Hinkka S, Anttila L, Grenman S, Klemi P, Härkönen P
Department of Anatomy and MediCity Research Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
Int J Cancer. 2000 Dec 1;88(5):718-25. doi: 10.1002/1097-0215(20001201)88:5<718::aid-ijc6>3.0.co;2-f.
FGF-8 is a mitogenic growth factor, which is widely expressed during embryonic development but only at a very low level in adult tissues. Alternative splicing of the human FGF-8 gene potentially allows coding for 4 protein isoforms (a, b, e, f), which differ in their transforming capacity. The FGF-8 isoforms preferentially activate the receptors FGFR1IIIc, FGFR2IIIc, FGFR3IIIc and FGFR4. FGF-8 is over-expressed in human breast and prostate cancers. Expression has also been found in RT-PCR studies of human ovarian and testicular cancers. The present study was undertaken to examine which FGF-8 isoforms are expressed in ovarian cancer and whether FGF-8 receptors are also expressed. Specimens from 5 normal human ovaries and 51 ovarian tumors (1 benign tumor, 8 borderline malignancies, 42 malignant tumors of different histopathological types) were studied by RT-PCR and immunohistochemistry. FGF-8 isoform b was expressed in all ovarian tumors and in all 7 ovarian-cancer cell lines studied. Isoform a was co-expressed in 9 malignant ovarian tumors. FGF-8 mRNA was not detected by RT-PCR of 3 normal ovary samples. Immunohistochemical staining localized FGF-8 protein to cancer cells. In general, the increased intensity of FGF-8 staining was associated with loss of differentiation within the tumors (Bowker's test, p = 0.37). FGF-8 staining of surface epithelium observed on 2 normal ovaries was very faint. RT-PCR showed that FGFR1IIIc, FGFR2IIIc and FGFR4 were the FGF-8 receptors expressed in normal ovaries and in ovarian tumors. FGF-8 receptor immunoreactivity was preferentially found in normal ovary surface epithelium and tumor cells but also in some stromal cells. Collectively, our results show that ovarian cancers of a wide variety of histological types expressing receptors for FGF-8 have acquired the capacity of expressing FGF-8. This suggests that FGF-8 has an important role in ovarian tumorigenesis.
成纤维细胞生长因子8（FGF - 8）是一种促有丝分裂生长因子，在胚胎发育过程中广泛表达，但在成年组织中仅以极低水平表达。人类FGF - 8基因的可变剪接可能编码4种蛋白质异构体（a、b、e、f），它们在转化能力上有所不同。FGF - 8异构体优先激活受体FGFR1IIIc、FGFR2IIIc、FGFR3IIIc和FGFR4。FGF - 8在人类乳腺癌和前列腺癌中过度表达。在对人类卵巢癌和睾丸癌的逆转录聚合酶链反应（RT - PCR）研究中也发现了其表达。本研究旨在检测卵巢癌中表达哪些FGF - 8异构体以及FGF - 8受体是否也有表达。通过RT - PCR和免疫组织化学对5例正常人类卵巢和51例卵巢肿瘤（1例良性肿瘤、8例交界性恶性肿瘤、42例不同组织病理学类型的恶性肿瘤）的标本进行了研究。FGF - 8异构体b在所有卵巢肿瘤以及所研究的全部7种卵巢癌细胞系中均有表达。异构体a在9例恶性卵巢肿瘤中共同表达。3例正常卵巢样本的RT - PCR未检测到FGF - 8信使核糖核酸（mRNA）。免疫组织化学染色将FGF - 8蛋白定位于癌细胞。总体而言，FGF - 8染色强度增加与肿瘤内分化丧失相关（Bowker检验，p = 0.37）。在2例正常卵巢上观察到的表面上皮的FGF - 8染色非常微弱。RT - PCR显示FGFR1IIIc、FGFR2IIIc和FGFR4是在正常卵巢和卵巢肿瘤中表达的FGF - 8受体。FGF - 8受体免疫反应性优先在正常卵巢表面上皮和肿瘤细胞中发现，但在一些基质细胞中也有发现。总体而言，我们的结果表明，多种组织学类型的卵巢癌表达FGF - 8受体，并已获得表达FGF - 8的能力。这表明FGF - 8在卵巢肿瘤发生中起重要作用。
