Expression and regulation of beta-defensin 11 in the oviduct in response to estrogen and in ovarian tumors of chickens

Abstract

Avian beta-defensins (AvBDs), also known as gallinacins, are small cationic peptides having three cysteine disulfide bonds between their cysteine residues. They play essential roles in the innate immune system as well as stimulate proliferation of epithelial cells and fibroblasts. Although we found the avian homolog of human beta-defensin 11 to be highly expressed in chicks treated with the diethylstilbestrol (DES, a synthetic estrogen agonist), little is known about the hormonal and transcriptional regulation of AvBD-11 in the chicken oviduct and its expression in cancerous ovaries of chickens. Results of this study of young chicks revealed that DES induced AvBD-11 mRNA and protein in the oviduct, specifically luminal and glandular epithelial cells. In addition, microRNA-1615 was discovered to influence AvBD-11 expression via its 3′-UTR which suggests post-transcriptional regulation of AvBD-11 expression in chickens. Furthermore, we compared the expression patterns of the AvBD-11 gene in normal and cancerous ovaries from laying hens which are models for human epithelial ovarian cancer. Our results demonstrated that AvBD-11 is most abundant in the glandular epithelium of endometrioid-type ovarian tumors, but not normal ovaries of laying hens. Collectively, these results suggest that AvBD-11 is an estrogen-induced gene during oviduct development and that it may be used as a biomarker for diagnosis of ovarian cancer and for monitoring effects of therapeutics on progression of ovarian carcinogenesis.