IDENTIFICATION OF A CELL-SURFACE GLYCOPROTEIN ASSOCIATED WITH NORMAL MAMMARY AND EXTRAMAMMARY EPITHELIAL-CELLS

The goal of the study was to identify any normal genes that may become inactivated in malignant cells, with associated modifications or loss of gene products. Consequently, attempts were made to identify such p roducts by generating monoclonal antibodies using an immune tolerisati on-immunisation procedure. Using such a technique, a plasma membrane-a ssociated glycoprotein with an apparent molecular weight of 92kDa was identified. The glycoprotein was termed luminal epithelial antigen (LE A.92). The pattern of expression of LEA.92 was demonstrated by an indi rect immunostaining technique. Using an in vitro model system represen ting various stages of breast oncogenesis, LEA.92 was detected on norm al or immortalised mammary epithelial cell (MEC) lines which were depe ndent on epidermal growth factor (EGF) and anchorage formation for gro wth and non-tumorigenic in nude mice. In contrast, LEA.92 was undetect able on oncogenically transformed or established lines of mammary carc inoma cell lines which were independent of EGF or anchorage formation for growth and were highly tumorigenic. The results appear to suggest a correlation between the down-regulation of LEA.92 and the developmen t of tumorigenicity in malignant MEC lines. Furthermore, the patterns of expression of LEA.92 on breast cells in tissue mirrored those of br east epithelial cells in cell cultures. LEA.92 was detected on the sur face of normal but not malignant epithelial cells, which included brea st, cervix, colon, lung, pancreas and stomach. LEA.92 appeared to be d istinct from receptor for epidermal growth factor, antigens associated with milk fat globule membrane and the family of epithelium-specific keratins.