Marsigliante S, Leo G, D'Elia M, Vinson G P, Greco S, Puddefoot J, Storelli C
Dipartimento di Biologia, Laboratorio di Fisiologia, Università di Lecce, Italy.
Eur J Cancer. 1994;30A(11):1694-700. doi: 10.1016/0959-8049(94)00334-2.
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.
通过高分辨率等电聚焦凝胶电泳（IEF），鉴定出两个他莫昔芬结合位点（TBS），其等电点（pI）值分别为4.5和4.3，对他莫昔芬具有不同的亲和力。pI为4.3的形式（HTBS）对配体显示出高亲和力（解离常数约为5 nM），而pI为4.5的蛋白质（LTBS）亲和力较低（解离常数约为50 nM）。LTBS存在于微粒体部分，HTBS存在于胞质溶胶中。在总共研究的319个肿瘤中，257个为雌激素受体（ER）阳性，106个为HTBS阳性。在这个能够通过存在ER或HTBS（或两者）结合他莫昔芬的联合组中，ER和PR与HTBS均呈负相关（P < 0.0001）。在319个肿瘤中的92个中检测了雌激素诱导蛋白pS2，其也与HTBS呈负相关（P < 0.0001）。无特殊特征的浸润性导管癌（NOS）和非NOS形式之间的HTBS水平相似。然而，3级低分化癌中的HTBS浓度明显高于2级（P < 0.05）和1级（P < 0.01）形式。相反，3级癌中的ER浓度低于1级形式（P < 0.05）。高亲和力TBS与ER之间的关系以及ER低表达的3级癌中HTBS的高浓度可能与已知的肿瘤对内分泌治疗反应和预后的变异性有关。
