Secreted frizzled related protein 1 is overexpressed in uterine leiomyomas, associated with a high estrogenic environment and unrelated to proliferative activity.
Secreted frizzled related protein 1 (sFRP1) is a modulator of Wnt signaling. Recently, aberrations of Wnt signaling were reported to be involved in the pathology of various human neoplasms. We investigated the expression and function of sFRP1 in uterine leiomyomas. Secreted FRP1 expression was increased in leiomyomas, compared with normal myometrium using Northern and Western blot analyses. Expression was strongest in the late follicular phase (high estrogenic milieu) of the menstrual cycle. Interestingly, expression was negligible in leiomyomas treated with GnRH agonist. Expression was also prominent in cells during E2 treatment, serum deprivation, and hypoxia. Moreover, induction of apoptosis by serum deprivation in a leiomyosarcoma cell line was enhanced by antisense inhibition of sFRP1. These results suggest that sFRP1 expression was associated with uterine leiomyomas, particularly under high estrogenic conditions. Secreted FRP1 expression was not associated with cell proliferation but rather occurred during cell protection against apoptosis in vitro. Strong sFRP1 expression under high estrogenic conditions seems to contribute to the development of uterine leiomyomas through the antiapoptotic effect of sFRP1, which appear to be independent of cell proliferation.
Fukuhara
Ken
K
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyoku, Kyoto 606-8507, Japan.
Kariya
Masatoshi
M
Kita
Masato
M
Shime
Hiroaki
H
Kanamori
Takanobu
T
Kosaka
Chika
C
Orii
Ayaka
A
Fujita
Jun
J
Fujii
Shingo
S
D000328:Adult; D015153:Blotting, Western; D002455:Cell Division; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007158:Immunologic Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099274:Frizzled-Related Proteins
D004958:Estradiol; D004967:Estrogens; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D011374:Progesterone; D012333:RNA, Messenger; D000099274:Frizzled-Related Proteins