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Title: Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D
Authors: Navarro Bosch, Domingo 
Doreste, Hilario
Cabrera, Juan J. 
Morales, Manuel
Diaz-Chico, JC 
Díaz-Chico, Bonifacio N. 
UNESCO Clasification: 32 Ciencias médicas
320101 Oncología
Keywords: Hormone Receptors
Resistance, et al
Issue Date: 1998
Journal: Breast Cancer Research and Treatment 
Abstract: [H-3]Tamoxifen Aziridine ([H-3]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [H-3]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [H-3]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [H-3]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [H-3]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [H-3]TAZ was partially inhibited by both estrogens and antiestrogens. When [H-3]E-2 was used instead of [H-3]TAZ, only an SS peak was detected. [H-3]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [H-3]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [H-3]TAZ binding was not associated with clinicopathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [H-3]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [H-3]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.
ISSN: 0167-6806
DOI: 10.1023/A:1006062510883
Source: Breast Cancer Research And Treatment[ISSN 0167-6806],v. 50 (2), p. 155-166
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