Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis

• Published in: Breast cancer research : BCR Vol. 2; no. 6; pp. 444 - 454
• Main Authors: Maaroufi, Y, Lacroix, M, Lespagnard, L, Journé, F, Larsimont, D, Leclercq, G
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.01.2000; National Library of Medicine - MEDLINE Abstracts; BioMed Central
• Subjects: Adsorption; Binding Sites; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - chemistry; Cell Nucleus - metabolism; Chromatography, Liquid; Cytosol - chemistry; Development and progression; Durapatite; Electrophoresis, Polyacrylamide Gel; Endopeptidases - metabolism; Estrogen; Female; Genetic aspects; Hot Temperature; Humans; Molecular Weight; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Osmolar Concentration; Peptide Fragments - analysis; Peptide Fragments - isolation & purification; Potassium Chloride; Primary Research; Protease Inhibitors - pharmacology; Protein Isoforms - analysis; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Structure, Tertiary; Receptors; Receptors, Estrogen - analysis; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Recombinant Proteins - analysis; Recombinant Proteins - metabolism; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Solvents; Tumor Cells, Cultured; Belgium
• ISSN: 1465-5411; 1465-542X; 1465-542X
• DOI: 10.1186/bcr92

Iodinated oestradiol-labeled oestrogen receptor (ER) isoforms devoid of amino-terminal ABC domains represent about two-thirds of the whole receptor population detected in cytosol samples from human breast cancers. This high frequency could not be ascribed to the expression of truncated mRNAs, or to the proteolysis of the native ER peptide at the time of homogenization or assay, suggesting an intracellular proteolysis. Free amino-terminal and ligand-binding domains maintained together within oligomeric structure(s); increase of ionic strength separated them. The amino-terminal region was consistently detected in the cell nucleus by specific immunohistochemistry leading to the concept of a potential intranuclear association between ER cleavage products and/or other regulatory proteins.