Manni A, Wright C
Endocrinology. 1984 Mar;114(3):836-9. doi: 10.1210/endo-114-3-836.
Numerous studies suggest a relationship between the action of hormones on their target tissues and the synthesis of polyamines. To evaluate the role of polyamines in the mediation of the effect of estrogen on the growth of experimental hormone-responsive mammary cancer, we investigated whether the cytotoxic effect of the antiestrogen tamoxifen could be rescued by exogenous administration of polyamines. When added to N-nitrosomethylurea-induced mammary tumors grown in soft agar in the presence of tamoxifen, putrescine, spermidine, and spermine were able to reverse the inhibitory effect of antiestrogens on colony formation in a dose-dependent fashion. In contrast, no effect on colony number was observed when polyamines were added in the absence of tamoxifen. These results indicate that in this system, the antitumor effect of tamoxifen is mediated through induction of polyamine depletion. Consequently, the data suggest that estrogens may stimulate mitogenesis of the N-nitrosomethylurea-induced mammary tumor through the polyamine pathway.
大量研究表明激素对其靶组织的作用与多胺合成之间存在关联。为评估多胺在介导雌激素对实验性激素反应性乳腺癌生长的影响中的作用，我们研究了抗雌激素他莫昔芬的细胞毒性作用是否可通过外源性给予多胺来挽救。当将腐胺、亚精胺和精胺添加到在含有他莫昔芬的软琼脂中生长的N-亚硝基甲基脲诱导的乳腺肿瘤时，它们能够以剂量依赖性方式逆转抗雌激素对集落形成的抑制作用。相比之下，在没有他莫昔芬的情况下添加多胺时，未观察到对集落数量的影响。这些结果表明，在该系统中，他莫昔芬的抗肿瘤作用是通过诱导多胺耗竭来介导的。因此，数据表明雌激素可能通过多胺途径刺激N-亚硝基甲基脲诱导的乳腺肿瘤的有丝分裂。
