Relationships between tamoxifen binding proteins in primary breast cancer biopsies.
Using high-resolution isoelectric focusing gel electrophoresis (IEF), two tamoxifen binding sites (TBS) with isoelectric point (pI) values of 4.5 and 4.3 were identified, with different affinities for tamoxifen. The form at pI 4.3 (HTBS) displayed high affinity for the ligand (kD approximately 5 nM), while the protein at pI 4.5 (LTBS) had lower affinity (kD approximately 50 nM). LTBS was found in the microsomal fraction and HTBS in the cytosol. Of a total of 319 tumours studied, 257 were oestrogen receptor (ER) positive and 106 HTBS positive. In this combined group, thus able to bind tamoxifen either through the presence of ER or HTBS (or both), ER and PR were both negatively correlated with HTBS (P < 0.0001). The oestrogen-induced protein pS2 was assayed in 92 of the 319 tumours, and was also negatively (P < 0.0001) correlated with HTBS. The levels of HTBS were similar between infiltrating ductal carcinomas without special features (NOS) and non-NOS forms. However, HTBS concentrations were significantly higher in poorly differentiated grade 3 carcinomas than grade 2 (P < 0.05) and grade 1 (P < 0.01) forms. Conversely, ER concentration was lower in grade 3 than grade 1 forms (P < 0.05). Both the relationship between high affinity TBS and ER and the high concentration of HTBS in ER-poor grade 3 carcinomas may have a bearing on the known variability of tumour response to endocrine therapy and prognosis.
Dipartimento di Biologia, Laboratorio di Fisiologia, Università di Lecce, Italy.
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Marsigliante
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Leo
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D'Elia
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Vinson
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Greco
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Puddefoot
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Storelli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000502:physiology; D001706:Biopsy; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011506:Proteins; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000378:metabolism*; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D004967:Estrogens; D009363:Neoplasm Proteins; D011506:Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen