ESTROGENS STIMULATE CELL-PROLIFERATION AND INDUCE SECRETORY PROTEINS IN A HUMAN-BREAST CANCER CELL-LINE (T47D)

ESTROGENS STIMULATE CELL-PROLIFERATION AND INDUCE SECRETORY PROTEINS IN A HUMAN-BREAST CANCER CELL-LINE (T47D)
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DOI:
10.1210/jcem-55-2-276
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发表时间:
1982-01-01
影响因子:
5.8
通讯作者:
ROCHEFORT, H
ROCHEFORT, H
中科院分区:
医学2区
文献类型:
--
作者:
CHALBOS, D;VIGNON, F;ROCHEFORT, H

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体外研究了雌二醇 (E2) 对来自 T47D 人乳腺癌细胞系的 2 个克隆亚系的影响。通过DNA测定、细胞计数和胸苷掺入评估细胞增殖。通过[35S]甲硫氨酸掺入和聚丙烯酰胺凝胶电泳,然后进行荧光照相,测定释放到细胞培养基中的蛋白质的合成速率。在含有雌激素和孕激素受体的克隆 11 中,雌二醇 (1-pM-1 nM) 在 6 天的滞后期后刺激细胞增殖 2 至 5 倍。在不添加胰岛素的情况下,用 1% 或 3% 胎牛血清观察到最大刺激。 E2 的作用是双相的,因为 E2 浓度 < 10 nM 时生长速率受到刺激,而浓度较高时则逐渐受到抑制。地塞米松、二氢睾酮、孕酮和 R5020[孕酮](1 nM 或 1 μM)不会改变细胞生长。抗雌激素他莫昔芬(1μM)抑制E2诱导的刺激并减少对照细胞的生长。雌激素还刺激 .apprx 的合成 2 至 3 倍。 60K MW 道尔顿蛋白被释放到培养基中。这种效果早在 E2 治疗的第 1 天就可见,并且用 0.1 nM E2 达到刺激平台。相比之下,在含有低浓度雌激素和孕激素受体的克隆8中,E2对细胞生长没有影响,并且略微刺激了55K蛋白质的合成。显然,E2在刺激.apprx的合成后,能够直接刺激人上皮性乳腺癌细胞的增殖。 60,000 道尔顿蛋白质释放到培养基中。
The effects of estradiol (E2) on 2 cloned sublines derived from the T47D human breast cancer cell line were studied in vitro. Cell proliferation was evaluated by DNA assay, cell counts and thymidine incorporation. The rate of synthesis of proteins released into the cell culture medium was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis, followed by fluorography. In clone 11, which contains estrogen and progesterone receptors, estradiol (1-pM-1 nM) stimulated cell proliferation 2- to 5-fold after a lag period of 6 days. Maximal stimulation was observed with 1 or 3% fetal calf serum and without added insulin. The effect of E2 was biphasic, since the growth rate was stimulated for E2 concentrations < 10 nM and then progressively inhibited for higher concentrations. Dexamethasone, dihydrotestosterone, progesterone and R5020 [promegesterone] (at 1 nM or 1 .mu.M) did not modify cell growth. The antiestrogen Tamoxifen (1 .mu.M) inhibited the E2-induced stimulation and decreased the growth of control cells. Estrogen also stimulated 2- to 3-fold the synthesis of .apprx. 60K MW dalton proteins which were released into the medium. This effect was seen as early as 1 day of E2 treatment, and a plateau of stimulation was reached with 0.1 nM E2. By contrast, in clone 8, which contains low concentrations of estrogen and progesterone receptors, E2 had no effect on cell growth and stimulated slightly the synthesis of a 55K protein. Evidently, E2 is able to directly stimulate the proliferation of human epithelial breast cancer cells after having stimulated the synthesis of .apprx. 60,000 dalton proteins released into the medium.