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

Claudia Marchetti, Hellen Dassen, Chamindie Punyadeera, Bert Delvoux, Iris Schulkens, Rick Kamps, Jan Klomp, Fred Dijcks, Anton De Goeij, Thomas D'Hooghe, Cleophas Kyama, Antwan Ederveen, Gerard Dunselman, Patrick Groothuis, Andrea Romano

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)2495-2508
Numero di pagine14
RivistaTHE AMERICAN JOURNAL OF PATHOLOGY
Volume177
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • endometrial cancer

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