EXPRESSION OF GLYCODELIN IN MCF-7 BREAST-CANCER CELLS INDUCES DIFFERENTIATION INTO ORGANIZED ACINAR EPITHELIUM

Glycodelin, a 28-kd human glycoprotein found in glandular epithelial c ells of endometrium and seminal vesicle, was originally considered spe cific for the reproductive tract. Glycodelin has significant amino-aci d sequence homology with beta-lactoglobulins from various species. We report herein the expression of glycodelin in normal and neoplastic gl andular epithelia outside the reproductive tract including breast, swe at glands, parabronchial glands, hidradenoma, and pancreatic cystadeno ma. The localization of glycodelin in highly differentiated acinar epi thelia led us to investigate a possible role for glycodelin in epithel ial organization. Transfection of glycodelin cDNA into MCF-7 breast ca ncer cells induced a dramatically altered growth behavior with formati on of acinar configurations and an inability to grow in semisolid medi a because of apoptosis. The glycodelin-expressing cells also displayed strongly up-regulated expression of markers of organized epithelia, s uch as cytokeratins 8 and 18 as well as E-cadherin, and changes in int racellular distribution of beta-catenin. The rate of proliferation was also suppressed. These results show that, besides being a product of glandular epithelial cells, expression of glycodelin is accompanied by the acquisition of a phenotype of organized glandular epithelium.