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 products by generating monoclonal antibodies using an immune tolerisation-immunisation procedure. Using such a technique, a plasma membrane-associated glycoprotein with an apparent molecular weight of 92 kDa was identified. The glycoprotein was termed luminal epithelial antigen (LEA.92). The pattern of expression of LEA.92 was demonstrated by an indirect immunostaining technique. Using an in vitro model system representing various stages of breast oncogenesis, LEA.92 was detected on normal or immortalised mammary epithelial cell (MEC) lines which were dependent on epidermal growth factor (EGF) and anchorage formation for growth and non-tumorigenic in nude mice. In contrast, LEA.92 was undetectable on oncogenically transformed or established lines of mammary carcinoma 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 development of tumorigenicity in malignant MEC lines. Furthermore, the patterns of expression of LEA.92 on breast cells in tissue mirrored those of breast epithelial cells in cell cultures. LEA.92 was detected on the surface of normal but not malignant epithelial cells, which included breast, cervix, colon, lung, pancreas and stomach. LEA.92 appeared to be distinct from receptor for epidermal growth factor, antigens associated with milk fat globule membrane and the family of epithelium-specific keratins.
Imam
S A
SA
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Stampfer
M R
MR
Yilmaz
A
A
Taylor
C R
CR
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; C086262:LEA-92 protein, human; D008562:Membrane Glycoproteins; D004815:Epidermal Growth Factor