Role of prolactin in growth of the rat mammary tumor MTW9.

Role of prolactin in growth of the rat mammary tumor MTW9.
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催乳素在大鼠乳腺肿瘤 MTW9 生长中的作用。

DOI:
10.1002/ijc.2910480120
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发表时间:
1991
影响因子:
6.4
通讯作者:
Hollander,VP
Hollander,VP
中科院分区:
医学1区
文献类型:
--
作者:
Platica,M;Doody,J;Mandeli,JP;Hollander,VP

文献摘要

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MTW9乳腺肿瘤的生长对卵巢切除术表现出不同程度的反应性,从敏感到抵抗。这个反应范围是从肿瘤接种到卵巢切除术的时间的函数,前提是催乳素(PRL)水平保持持续高水平。体内研究表明,长期给予螺旋酰胺的MTW9肿瘤在60天内对卵巢切除术敏感,但在100天内对卵巢切除术产生抗性。然而,当肿瘤出现后停止螺旋胺治疗时,肿瘤在100天内仍然对卵巢切除术敏感。胞浆雌激素受体(ER)的色谱分离(CF)谱与卵巢切除术的反应性相关。观察到对卵巢切除术敏感的肿瘤的双峰曲线,而对卵巢切除术耐药的肿瘤仅为单峰曲线。尽管荷瘤大鼠的催乳素水平高于正常大鼠,但PRL水平与ER CF曲线随时间的变化之间没有相关性。此外,这些变化与肿瘤大小无关。体外研究表明,来自敏感肿瘤的胞质ER(2个峰)与PRL的孵育导致仅具有一个峰的CF谱,这是耐药肿瘤的特征。亮抑酶肽、苯甲磺酰氟和苯甲磺酰氟(PMSF)不能阻止这种转变。与生长激素或孕酮孵育的效果没有再现。我们的数据表明,催乳素,无论是直接或通过中间体,可能发挥作用,改变乳腺肿瘤MTW9的激素治疗的反应。
The growth of MTW9 mammary tumors exhibits different degrees of responsiveness to ovariectomy, ranging from sensitivity to resistance. This range of response is a function of time elapsing from tumor inoculation until performance of ovariectomy provided that prolactin (PRL) level is kept continuously high. In vivo studies showed that the MTW9 tumors developed by chronic administration of spiramide were sensitive to ovariectomy by 60 days, but they became resistant to ovariectomy by 100 days. However, when spiramide treatment was discontinued after tumor appearance, the tumors were still sensitive to ovariectomy by 100 days. Chromatofo‐cusing (CF) profile of cytosolic estrogen receptors (ER) correlated with the responsiveness to ovariectomy. A 2‐peak profile for tumors sensitive to ovariectomy, and only a one‐peak profile for tumors resistant to ovariectomy, were seen. Although the prolactin level in rats bearing the tumors was higher than in the normal rats, no correlation between the PRL level and the change in CF profile of ER over time was seen. Also, these changes could not be correlated with the tumor size. In vitro studies showed that incubation of cytosolic ER from a sensitive tumor (2 peaks) with PRL led to a CF profile with only one peak, characteristic of a resistant tumor. Leupeptin, molybdate and phenylmethylsulfonylfluoride (PMSF) could not prevent this transition. The effect was not reproduced by incubation with growth hormone or progesterone. Our data suggest that PRL, either directly or through intermediates, may play a role in changing the response to hormonal therapy of the mammary tumor MTW9.