MAMMARY-DERIVED GROWTH INHIBITOR (MDGI) CLONED FROM HUMAN BREAST EPITHELIAL-CELLS IS EXPRESSED IN FULLY DIFFERENTIATED LOBULAR STRUCTURES

Mammary-derived growth inhibitor (MDGI), an inducer of rodent mammary differentiation and suppressor of human breast cancer cell growth, has been cloned from bovine and rodent mammary glands. The present study reports the cloning of MDGI from cultured human breast epithelial cell s (HBEC-MDGI) as a cDNA fragment encoding a protein of 133 amino acids identical to heart fatty acid binding protein. Expression of HBEC-MDG I, as detected by in situ hybridization in paraffin-embedded normal br east tissues, was maximal in the most differentiated lobules type 4, l ow in the moderately differentiated lobules type 3, and absent in the least differentiated lobules types 1 and 2. HBEC-MDGI was not expresse d in breast tissues that contained ductal hyperplasia, carcinoma in si tu or invasive carcinomas. Our results indicate that HBEC-MDGI is a bi omarker of lobular differentiation in the human breast, and its expres sion is silenced in poorly differentiated lobules as well as in the ea rly and late stages of breast cancer progression.