Biosynthesis of MUC1 mucin in human endometrial adenocarcinoma is modulated by estradiol and tamoxifen.
Polymorphic epithelial mucin MUC1 is expressed by most epithelial cancers, although free natural MUC1 antibodies are present in the circulation of healthy subjects as well as in that of cancer patients. The role of MUC1 mucin molecules in cancer cells of endometrium is not precisely known. The results reported here demonstrate that MUC1 biosynthesis in human endometrial adenocarcinoma cells (Ishikawa line) is stimulated by estradiol hormone and inhibited by tamoxifen, which was measured by [(14)C]threonine or [(3)H]glucosamine incorporation into MUC1 protein. Tamoxifen applied in combination with estradiol also inhibited this process, but pre-incubation of cells with estradiol resulted in a decrease in the inhibitory effect of tamoxifen. Electroblotting and reactions with antibodies against MUC1 core protein epitopes confirmed the presence of MUC1 in cell lysates and culture media of Ishikawa cells. Reactions with lectins showed the presence of oligosaccharide structures demonstrating antigen-T activity and the presence of sialic acid residues. The results confirm that there is downregulation of MUC1 expression in cancer culture cells treated with selective estrogen receptor modulators, which may be essential for reducing the migration of cancer cells and the metastatic properties of tumor cells.
Department of Medical Chemistry, Medical Academy, Białystok, Poland.
A
A
Paszkiewicz-Gadek
H
H
Porowska
T
T
Anchim
S
S
Wołczyński
A
A
Gindzieński
D000230:Adenocarcinoma / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D002250:Carbon Radioisotopes; D004591:Electrophoresis, Polyacrylamide Gel; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005944:Glucosamine / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D037102:Lectins; D018396:Mucin-1 / Q000096:biosynthesis* / Q000302:isolation & purification; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D013912:Threonine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002250:Carbon Radioisotopes; D037102:Lectins; D018396:Mucin-1; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D014316:Tritium; D013912:Threonine; D004958:Estradiol; D005944:Glucosamine