Expression of fibroblast growth factor (FGF)-8 isoforms and FGF receptors in human ovarian tumors.

Abstract

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.

• Authors: E Valve, P Martikainen, J Seppänen, S Oksjoki, S Hinkka, L Anttila, S Grenman, P Klemi, P Härkönen
• Journal: International journal of cancer (Int J Cancer) Vol. 88 Issue 5 Pg. 718-25 (Dec 01 2000) ISSN: 0020-7136 [Print] United States
• PMID: 11072239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• FGF8 protein, human
• Protein Isoforms
• RNA, Messenger
• Receptors, Fibroblast Growth Factor
• Fibroblast Growth Factor 8
• Fibroblast Growth Factors

Topics

• Adult
• Aged
• Aged, 80 and over
• Blotting, Southern
• Female
• Fibroblast Growth Factor 8
• Fibroblast Growth Factors (analysis, biosynthesis, genetics, metabolism)
• Humans
• Immunohistochemistry
• Middle Aged
• Ovarian Neoplasms (metabolism, pathology)
• Protein Isoforms (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Receptors, Fibroblast Growth Factor (biosynthesis, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured