SVEP1 expression is regulated in estrogen-dependent manner.

The SVEP1 protein comprises modules related to the selectin super family and other motifs found in cell surface molecules. Earlier, we demonstrated that SVEP1 is expressed in osteogenic cells both in vivo and in vitro; in the current study we elaborate on the regulation of SVEP1 by 17beta-Estradiol (17betaE2). SVEP1 message is expressed in vivo by bone marrow cells of sham-operated rats, but not in estrogen-depleted ovariectomized (OVX) rats. We demonstrated that 17betaE2 treatment increases the level of the SVEP1 expression in cultured osteoblasts. SVEP1 was identified also in breast carcinoma (BC) cells known to reside in bone when metastasized from the primary tumor. SVEP1 expression was demonstrated by immunohistochemistry and fluorescence-activated cell sorting (FACS) on various BC cell lines. The chromatin immunoprecipitation (ChIP) assay was applied to analyze the estrogen receptor (ER) binding to the putative SVEP1 promoter. We demonstrated that treatment with 17betaE2 or ICI 182,780 affects this binding and regulates the mRNA and protein levels of SVEP1 in BC cells. We propose that SVEP1 may serve as a useful biomarker for studying the mechanism of cells interactions within the local microenvironment affected by estrogen. Copyright 2006 Wiley-Liss, Inc.