Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice.
Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice.
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发表时间：
1985-02
期刊：
影响因子：
11.2
通讯作者：
C. Osborne;K. Hobbs;G. Clark
中科院分区：
文献类型：
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作者：
C. Osborne;K. Hobbs;G. Clark
雌激素剥夺或抗雌激素的内分泌治疗导致部分晚期乳腺癌患者的肿瘤消退。为了更好地了解雌激素和抗雌激素在体内调节乳腺癌生长的机制，我们研究了内分泌调控对无胸腺裸鼠中培养的人乳腺癌细胞来源的肿瘤发生和生长的影响。将MCF-7乳腺癌细胞接种到6周龄雌性BALB/c无胸腺裸鼠中。切除卵巢的小鼠中没有发生肿瘤生长。然而，细胞仍然存活，因为 30 多天后补充雌激素导致肿瘤形成。在循环雌激素水平较低的完整雌性裸鼠中观察到最小的肿瘤生长。补充了皮下注射形式的 17 β-雌二醇的切除卵巢或完整小鼠中的肿瘤发育和生长。颗粒具有剂量依赖性；雌激素剂量在 0.01 至 0.5 毫克之间时，生长速度加快。他莫昔芬或 LY156758 的抗雌激素治疗引起肿瘤生长的短暂刺激，随后是延长的静止期。通过补充雌激素恢复生长。用雌激素撤除（去除雌激素颗粒）对携带已建立的MCF-7肿瘤的小鼠进行治疗导致肿瘤生长停止，但没有使肿瘤消退。抗雌激素也观察到生长抑制，并且是剂量依赖性的。然而，即使在用高剂量他莫昔芬（血清浓度为1.0μM）治疗长达60天的小鼠中，肿瘤也没有发生消退。通过补充雌激素，这些小鼠的肿瘤生长得以恢复。尽管长期（1个月）雌激素剥夺或抗雌激素治疗，肿瘤细胞在组织学上仍然保持活力，尽管有丝分裂指数显着降低。对接种激素反应性 ZR75-1 人乳腺癌细胞的小鼠进行了类似的观察，但对接种不受雌激素或抗雌激素治疗影响的激素非依赖性 MDA-231 细胞的小鼠进行了类似的观察。综上所述，裸鼠MCF-7和ZR75-1肿瘤的发生和生长具有雌激素依赖性。通过雌激素剥夺或抗雌激素治疗进行的内分泌治疗可抑制裸鼠肿瘤细胞增殖，但不会导致肿瘤消退或细胞活力丧失。
Endocrine therapy with estrogen deprivation or with antiestrogens results in tumor regression in a subset of patients with advanced breast cancer. To better understand the mechanisms by which estrogens and antiestrogens modulate breast cancer growth in vivo, we have studied the effects of endocrine manipulation on the development and growth of tumors derived from cultured human breast cancer cells in the athymic nude mouse. MCF-7 breast cancer cells were inoculated into 6-week-old female BALB/c athymic nude mice. Tumor growth did not occur in ovariectomized mice. Cells remained viable, however, since estrogen supplementation more than 30 days later resulted in tumor formation. Minimal tumor growth was observed in intact female nude mice which have low circulating estrogen levels. Tumor development and growth in ovariectomized or intact mice supplemented with 17 beta-estradiol in the form of a s.c. pellet were dose dependent; growth rates increased with estrogen doses ranging from 0.01 to 0.5 mg. Antiestrogen treatment with either tamoxifen or LY156758 caused transient stimulation of tumor growth, followed by a prolonged stationary phase. Growth resumed with estrogen supplementation. Treatment of mice bearing established MCF-7 tumors with estrogen withdrawal (removal of estrogen pellet) resulted in cessation of tumor growth, but not in tumor regression. Growth inhibition was also observed with antiestrogens and was dose dependent. However, tumor regression did not occur, even in mice treated with high doses of tamoxifen (serum concentration of 1.0 microM) for as long as 60 days. Tumor growth was restored in these mice with estrogen replenishment. Tumor cells also remained viable histologically despite prolonged (1 month) estrogen deprivation or antiestrogen therapy, although the mitotic index was markedly reduced. Similar observations were made with mice inoculated with the hormone-responsive ZR75-1 human breast cancer cells, but not with hormone-independent MDA-231 cells which were not influenced by estrogen or antiestrogen treatment. In summary, development and growth of MCF-7 and ZR75-1 tumors in nude mice are estrogen dependent. Endocrine therapy by estrogen deprivation or antiestrogen treatment inhibits tumor cell proliferation in nude mice, but does not cause tumor regression or loss of cell viability.