Results
PMID | 21048224 |
Gene Name | OLFM4 |
Condition | Endometriosis |
Association |
Associated |
Sex | Female |
Other associated phenotypes |
Endometriosis |
Am J Pathol. 2010 Nov;177(5):2495-508. doi: 10.2353/ajpath.2010.100026. 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| Ro GROW--School for Oncology and Developmental Biology, Department of Pathology, Maastricht University and Medical Centre, 6202 AZ, Maastricht, The Netherlands. 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 17beta-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 17beta-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 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. Mesh Terms: Adult| Aged| Aged, 80 and over| Apoptosis| Cell Adhesion| Cells, Cultured| Endometrial Neoplasms/metabolism/pathology| Endometriosis/metabolism| Endometrium/cytology/pathology/*physiology| Epidermal Growth Factor/*metabolism| Estrogens/*metaboli |