Abstract
Abstract
Commonly diagnosed in reproductive-age women, endometriosis is causally linked to subfertility, infertility, and chronic pelvic pain. Although theories exist on the etiopathogenesis of endometriosis, our understanding of its cellular and molecular underpinnings remain incomplete. We report that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is expressed predominantly in epithelial cells of ectopic endometriotic lesions in the primate and mouse. Using an immortalized human endometriosis epithelial cell (iHEEC) line in conjunction with siRNA-mediated silencing, we demonstrate that SRC-2 is essential for many of the pathogenic features ascribed to endometriotic lesion expansion, including sustained viability along with clonogenic, migratory, and invasive properties. Genome-scale iHEEC RNA-seq analysis implicates SRC-2 in a number of pathobiologies associated with the cellular phenotype of the ectopic endometriotic epithelial cell, including actin-cytoskeleton reorganization. To underscore the utility of this RNA-seq dataset, we show that S100A10, a cytoarchitectural scaffolding protein, is responsive to SRC-2 and essential for many of above cellular properties of the iHEEC that are ascribed to SRC-2. Because S100A10 dysregulation is strongly linked to the etiopathogenesis of a wide-spectrum of malignancies, many of the molecular mechanisms which underlie S100A10’s role in cancer progression are predicted to be coopted in endometriosis. Therefore, these investigations highlight an unsuspected role for SRC-2 (and its transcriptome) in maintaining the pathogenetic phenotype of the ectopic endometriotic epithelial cell. Such findings, support continued investigations of this coactivator and its downstream gene expression programs as potential targets for the prognosis, diagnosis and/or treatment of this gynecological disorder in the future.