Expression of glycodelin in human breast and breast cancer

Glycodelin is a 28 kDa glycoprotein with structural homology to beta-lactog lobulins, particularly expressed in steroid-responsive tissues of the femal e reproductive tract. We previously found that transfection of glycodelin c DNA into MCF-7 breast cancer cells induces differentiation into organized a cinar epithelium and up-regulation of epithelial markers, In this study, we used immunohistochemistry, Northern blotting and reverse transcription-pol ymerase chain reaction (RT-PCR) analyses to study glycodelin expression in normal and in malignant breast tissues. The results were compared with the expression of estrogen (ER) and progesterone receptors (PR) and p53 tumor s uppressor protein. Glycodelin was found in ductal and lobular epithelium of 6/6 normal breast: tissues, 27/29 morphologically normal breast tissues fr om breast cancer patients, 6/6 benign lactating adenomas, 21/35 ductal carc inomas, 9/9 tubular carcinomas, 9/9 mucinous carcinomas, 3/3 mixed ductal/t ubular carcinomas and 7/11 lobular carcinomas. In the tatter, of particular interest was the presence of glycodelin In paranucleolar vacuoles of carci noma cells. Northern blot analysis of fresh frozen tissues revealed the nor mal full length 0.9 kb mRNA of glycodelin in ductal breast carcinoma, Using RT-PCR analysis, glycodelin messenger ribonucleic acid was found in 13/13 ductal and in 3/3 tubular tumor tissues. We also detected a splicing varian t lacking exon 4, which includes the nucleotide sequence encoding the poten tial N-glycosylation site at Asn-85, Our results demonstrate the synthesis of glycodelin in normal breast and breast cancer. In addition, we show that the paranuclear vacuole, characteristically present in lobular breast canc er cells, contains abundant amounts of glycodelin. (C) 1999 Wiley-Liss, Inc .