Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling

Dassen, Hellen, Punyadeera, Chamindie, Delvoux, Bert, Schulkens, Iris, Marchetti, Claudia, Kamps, Rick, Klomp, Jan, Dijcks, Fred, de Goeij, Anton, D'Hooghe, Thomas, Kyama, Cleophas, Ederveen, Antwan, Dunselman, Gerard, Groothuis, Patrick and Romano, Andrea (2010) Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling. American Journal of Pathology, 177 5: 2495-2508. doi:10.2353/ajpath.2010.100026

Author Dassen, Hellen
Punyadeera, Chamindie
Delvoux, Bert
Schulkens, Iris
Marchetti, Claudia
Kamps, Rick
Klomp, Jan
Dijcks, Fred
de Goeij, Anton
D'Hooghe, Thomas
Kyama, Cleophas
Ederveen, Antwan
Dunselman, Gerard
Groothuis, Patrick
Romano, Andrea
Title Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
Publication date 2010-11
Sub-type Article (original research)
DOI 10.2353/ajpath.2010.100026
Volume 177
Issue 5
Start page 2495
End page 2508
Total pages 14
Place of publication Bethesda, M.D., U.S.A.
Publisher American Society for Investigative Pathology
Collection year 2011
Language eng
Abstract Olfactomedin-4 (OLFM-4) is an extracellular matrix protein that is highly expressed in human endometrium. We have examined the regulation and function of OLFM-4 in normal endometrium and in cases of endometriosis and endometrial cancer. OLFM-4 expression levels are highest in proliferative-phase endometrium, and 17β-estradiol up-regulates OLFM-4 mRNA in endometrial explant cultures. Using the luciferase reporter under control of the OLFM-4 promoter, it was shown that both 17β-estradiol and OHtamoxifen induce luciferase activity, and epidermal growth factor receptor-1 is required for this estrogenic response. In turn, EGF activates the OLFM-4 promoter, and estrogen receptor-α is needed for the complete EGF response. The cellular functions of OLFM-4 were examined by its expression in OLFM-4-negative HEK-293 cells, which resulted in decreased vimentin expression and cell adherence as well as increased apoptosis resistance. In cases of endometriosis and endometrial cancer, OLFM-4 expression correlated with the presence of epidermal growth factor receptor-1 and estrogen receptor-α (or estrogen signaling). An increase of OLFM-4 mRNA was observed in the endometrium of endometriosis patients. No change in OLFM-4 expression levels were observed in patients with endometrial cancer relative with controls. In conclusion, cross-talk between estrogen and EGF signaling regulates OLFM-4 expression. The role of OLFM-4 in endometrial tissue remodeling before the secretory phase and during the predisposition and early events in endometriosis can be postulated but requires additional investigation. Copyright © American Society for Investigative Pathology.
Keyword Olfactomedin-4 (OLFM-4)
epidermal growth factor receptor-1
estrogenic response
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Created: Thu, 25 Nov 2010, 12:50:36 EST by Maria Campbell on behalf of School of Chemical Engineering