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

Dassen, H., Punyadeera, Chamindie, Delvoux, B., Schulkens, I., Marchetti, C., Kamps, R., Klomp, J., Dijcks, F., de Goeij, A., D'Hooghe, T., Kyama, C., Ederveen, A., Dunselman, G., Groothuis, P., & Romano, A. (2010) Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling. American Journal of Pathology, 177(5), pp. 2495-2508.

View at publisher


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 17 beta-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 17 beta-estradiol and OH-tamoxifen 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-alpha 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-alpha (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 controts. 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. (Am J Pathol 2010, 177:2495-2508: DOI: 10.2353/ajpath.2010.100026

Impact and interest:

12 citations in Scopus
Search Google Scholar™
12 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 77879
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Additional URLs:
Keywords: gene-expression, menstrual-cycle, gastric-carcinoma, serial analysis, receptor, protein, cells, cancer, hgc-1, kinase
DOI: 10.2353/ajpath.2010.100026
ISSN: 1525-2191
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright © 2010 American Society for Investigative Pathology
Deposited On: 22 Oct 2014 04:23
Last Modified: 23 Oct 2014 01:09

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page