Scala D A, Ip M M
Cancer Res. 1987 Aug 15;47(16):4287-92.
Estrogen-binding proteins have been characterized in variants of the MTW-9B rat mammary tumor in an attempt to determine the functional significance of the low affinity cytosolic estrogen binder. In vivo selection of tumor variants was carried out by transplant of the tumor into intact and castrated male and female Wistar-Furth rats for four or five successive transplant generations. Tumors that developed in each of the four lines were taken for retransplant into intact and castrated male and female rats and all recipient tumor groups were compared for high and low affinity estrogen-binding proteins using isoelectric focusing analysis. No alterations in the isoelectric focusing profiles were observed in tumors that developed after repeated passage in ovariectomized female or castrated male rats when compared to the profile of the estrogen-binding proteins of the parent tumor carried routinely in intact female rats. However, a tumor variant containing only the low affinity, more basic estrogen-binding protein resulted from repeated passage of the MTW-9B mammary tumor in male rats. The high affinity estrogen receptor was absent in this variant and could not be induced by retransplant of the tumor into intact female hosts. Growth of the parent tumor and each of the variants was shown to be ovarian independent, suggesting that the presence of the low affinity estrogen-binding protein is not predictive of estrogen responsiveness. This suggestion is further supported by the observation that estrogen-stimulated progesterone receptor synthesis could be demonstrated in the parent tumor which demonstrated both binders, but not in the tumor variant developed in male rats which contained only the low affinity estrogen-binding protein. Progesterone receptor synthesis in this latter tumor appeared to be constitutive. Studies are continuing in an attempt to identify a role for the cytosolic low affinity estrogen-binding protein.
为了确定低亲和力胞质雌激素结合蛋白的功能意义，已对MTW - 9B大鼠乳腺肿瘤的变体中的雌激素结合蛋白进行了表征。通过将肿瘤连续四五代移植到完整的和去势的雄性和雌性Wistar - Furth大鼠体内，对肿瘤变体进行体内筛选。将四个品系中形成的肿瘤再次移植到完整的和去势的雄性和雌性大鼠体内，并使用等电聚焦分析比较所有受体肿瘤组中高亲和力和低亲和力雌激素结合蛋白的情况。与常规保存在完整雌性大鼠体内的亲本肿瘤的雌激素结合蛋白谱相比，在卵巢切除的雌性大鼠或去势的雄性大鼠中反复传代后形成的肿瘤，其等电聚焦图谱没有变化。然而，MTW - 9B乳腺肿瘤在雄性大鼠中反复传代后产生了一种仅含有低亲和力、碱性更强的雌激素结合蛋白的肿瘤变体。该变体中不存在高亲和力雌激素受体，将该肿瘤再次移植到完整雌性宿主中也无法诱导其产生。亲本肿瘤和每个变体的生长都显示为卵巢非依赖性，这表明低亲和力雌激素结合蛋白的存在并不能预测雌激素反应性。这一观点进一步得到以下观察结果的支持：在同时具有两种结合蛋白的亲本肿瘤中可证明雌激素刺激的孕酮受体合成，但在仅含有低亲和力雌激素结合蛋白的雄性大鼠中形成的肿瘤变体中则未观察到。后一种肿瘤中的孕酮受体合成似乎是组成性的。目前仍在继续研究，试图确定胞质低亲和力雌激素结合蛋白的作用。
