Moncharmont B, Ramp G, De Goeij C C, Sluyser M
Istituto di Patologia Generale ed Oncologia, Prima Facoltà di Medicina e Chirurgia, Università di Napoli, Italy.
Cancer Res. 1991 Aug 1;51(15):3843-8.
Hormone-dependent (HD) Grunder strain mouse mammary carcinomas contain a 65-kDa estrogen receptor (ER) with minor amounts of 50- and 35-kDa components which apparently still contain the intact hormone-binding (COOH-terminal) domain. When the HD tumors lose their hormonal dependence during serial transplantation, the hormone-independent (HI) transplants show an increase in 50- and 35-kDa components relative to 65-kDa ER. In HI transplants of three of five tumor lines studied (TSl 85, 86, and 106), the 65-kDa receptor was entirely replaced by 50- and 35-kDa receptors, whereas in the two other lines (TSl 101 and 104) there usually were about equal amounts of 65- and 50-kDa ERs. No difference was found between ERs of HD and HI tumors in affinity for estradiol, steroid specificity, or immunoreactivity for the monoclonal antibody JS34/32. Estrogen stimulation of HI tumors did not increase the concentration of progesterone receptor in the tumor tissue, indicating that ER in these tumors was not functional in enhancing progesterone receptor. Incubation of 65-kDa ER with HI tumor cytosol or combined homogenization of HD and HI tumor tissue did not cause degradation of 65-kDa ER. alpha-Chymotrypsin-like protease activity generally was lower in HI than in HD tumor cytosols, indicating that the lower molecular size of ER in HI tumors cannot be attributed to the increased level of this protease activity.
激素依赖性(HD)格鲁德品系小鼠乳腺癌含有一种65千道尔顿的雌激素受体(ER),还有少量50千道尔顿和35千道尔顿的成分,这些成分显然仍含有完整的激素结合(羧基末端)结构域。当HD肿瘤在连续传代移植过程中失去激素依赖性时,激素非依赖性(HI)移植瘤相对于65千道尔顿的ER,50千道尔顿和35千道尔顿的成分有所增加。在所研究的五个肿瘤系中的三个(TSl 85、86和106)的HI移植瘤中,65千道尔顿的受体完全被50千道尔顿和35千道尔顿的受体取代,而在另外两个系(TSl 101和104)中,65千道尔顿和50千道尔顿的ER含量通常大致相等。HD和HI肿瘤的ER在对雌二醇的亲和力、类固醇特异性或对单克隆抗体JS34/32的免疫反应性方面没有差异。雌激素刺激HI肿瘤并没有增加肿瘤组织中孕酮受体的浓度,这表明这些肿瘤中的ER在增强孕酮受体方面不起作用。用HI肿瘤细胞溶胶孵育65千道尔顿的ER,或对HD和HI肿瘤组织进行联合匀浆处理,均未导致65千道尔顿的ER降解。HI肿瘤细胞溶胶中的α-糜蛋白酶样蛋白酶活性通常低于HD肿瘤细胞溶胶,这表明HI肿瘤中ER分子尺寸较小并非归因于这种蛋白酶活性水平的升高。