Premium
Expression of fibroblast growth factor (FGF)‐8 isoforms and FGF receptors in human ovarian tumors
Author(s) -
Valve Eeva,
Martikainen Paula,
Seppänen Jani,
Oksjoki Sanna,
Hinkka Susanna,
Anttila Leena,
Grenman Seija,
Klemi Pekka,
Härkönen Pirkko
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001201)88:5<718::aid-ijc6>3.0.co;2-f
Subject(s) - fibroblast growth factor , biology , immunohistochemistry , fibroblast growth factor receptor , ovarian cancer , receptor , ovary , cancer , cancer research , fibroblast growth factor receptor 1 , endocrinology , medicine , pathology , immunology , biochemistry , genetics
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. Int. J. Cancer 88:718–725, 2000. © 2000 Wiley‐Liss, Inc.