Major molecular weight heterogeneity of estrogen receptor from breast cancer is not related to neoplasia.
Recent investigation from our laboratory revealed that the estrogen receptor (ER) from breast cancer is characterized by a high molecular weight polymorphism: SDS-polyacrylamide gel electrophoresis of [3H]-tamoxifen aziridine ([3H]-TAZ) labeled cytosols usually display several bands corresponding to the native receptor (67 KDa) and lower molecular cleavage products. High frequency of such altered receptors was confirmed here by size exclusion FPLC of [125I]-E2 labeled cytosols from a series of 98 breast cancers: on the average, 60% of the ER molecules were strongly degraded (Mr < or = 37 KDa). The absence of transcriptional activating domains (ABC domains) in such receptors was further demonstrated by assessing their ability to bind to hydroxylapatite (HAP). Thus, in presence of 500 mM KCI, 55% of ERs from another series of 54 cytosols failed to strongly adsorb to this phosphocalcic matrix, a characteristic property of receptors without exposed ABC domains. Finally, [3H]-TAZ labeled cytosols from normal uterine tissue and MCF-7 human breast cancer cells growing in nude mice displayed identical multibands electrophoretic patterns revealing in both cases native and cleaved receptors. Since latter receptor forms were never detected in MCF-7 cells growing in monolayer culture, we put forward the hypothesis that they were produced under the action of proteolytic enzymes acting at the time of tissue processing. Hence, most of the truncated receptors detected in human breast cancer cytosols should not be markers of malignancy.
Maaroufi
Y
Y
Laboratoire J.-C. Heuson de Cancérologie Mammaire, Institut Jules Bordet, Brussels (Belgium), USA.
Trivedi
S
S
Leclercq
G
G
D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry*; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000302:isolation & purification; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000737:chemistry
D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; C031859:tamoxifen aziridine