Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding.
Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-related bleeding. These findings support the role of the bFGF ligand-receptor system in the pathogenesis of leiomyoma-related bleeding and may have implications for fertility and contraception since the differential FGFR1 expression occurs in the peri-implantation period of the early luteal phase.
Anania
C A
CA
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Stewart
E A
EA
Quade
B J
BJ
Hill
J A
JA
Nowak
R A
RA
D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D017931:DNA Primers; D004717:Endometrium / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008598:Menstruation; D008875:Middle Aged; D008969:Molecular Sequence Data; D009215:Myometrium / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D017697:Premenopause; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D012016:Reference Values; D014592:Uterine Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014599:Uterus / Q000378:metabolism* / Q000473:pathology
D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1