Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling.
We used an animal model to study uterine leiomyoma in the context of pregnancy-associated changes in gene expression and to determine how they might modulate tumor growth. Spontaneous tumors and normal myometrium were collected from Eker rats and compared with myometrial samples from pregnant animals. A leiomyoma-derived cell line was also used to assess pregnancy-related changes in gene expression and to determine the impact of signaling by the oxytocin receptor. Eker rat leiomyomas expressed several pregnancy-related genes, including connexin 43, oxytocin receptor (OTR), and cyclooxygenase (COX)-1; however, the tumors did not express COX-2, which is expressed in the parturient myometrium. The leiomyoma-derived cell lines also expressed OTR, which responds to estrogen, binds to oxytocin, and exhibits a calcium flux when stimulated with oxytocin. The OTR signaling mediated by oxytocin inhibited estrogen-stimulated growth of leiomyoma cells. Leiomyoma cells expressed many genes of the parturient myometrium, including OTRs, but were deficient in COX-2 expression. Signaling via the OTR appears to inhibit estrogen-induced cell proliferation, suggesting that signaling by this receptor might help mediate the protective effect of pregnancy on this disease.
Cesen-Cummings
Kimberley
K
Laboratory of Women's Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Houston
Kevin D
KD
Copland
John A
JA
Moorman
Valerie J
VJ
Walker
Cheryl Lyn
CL
Davis
Barbara J
BJ
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics; D007889:Leiomyoma / Q000737:chemistry*; D008565:Membrane Proteins; D009215:Myometrium / Q000737:chemistry*; D010121:Oxytocin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018045:Receptors, Oxytocin / Q000235:genetics*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000737:chemistry*
D018031:Connexin 43; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D004958:Estradiol; D010121:Oxytocin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone