HUGGINS C, MAINZER K, TORRALBA Y
J Exp Med. 1956 Oct 1;104(4):525-38. doi: 10.1084/jem.104.4.525.
A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic. The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added. In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions. In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor. In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of growth of the tumor until a peak was achieved; an increase of the dose above the optimal amount depressed the growth of the tumor. The stage of depression of growth was not observed in the mammary glands of these tumor-bearing rats. Many steroids which induced gestational changes in the mammary gland accelerated the growth of the tumor. Among these were estrone and progesterone in combination and 17alpha-ethinyl-19-nor-testosterone administered alone. But gestational changes developed in the mammary gland of rats treated with 4-androstene-3alpha,17beta-diol, without growth of the tumor. The evidence which we have presented proves that the mammary fibroadenoma tested had some of the functional properties of a normal mammary gland, and neoplastic traits as well. In its response to hormones it had characteristics which set it apart from all other endocrine targets of the rat.
在95%的成年未阉割雌性大鼠中，移植的乳腺纤维腺瘤能够生长，肿瘤重量的增加呈渐进性且为对数增长。卵巢切除可抑制肿瘤生长，若同时进行肾上腺切除，抑制作用更强。在去卵巢大鼠中，酚类雌激素可刺激肿瘤生长，添加孕酮后这种增长会增强。在对激素变化的这些反应中，乳腺和肿瘤表现相似。然而，纤维腺瘤的生长与乳腺的生长存在许多差异。与成年未阉割雌性大鼠中出现的渐进性生长不同，垂体切除术后大鼠移植瘤有一段较长的惰性生长期；但数周后开始活跃生长，肿瘤最终长得很大。在静止生长期间，肿瘤在细胞学上呈萎缩状态，但生长加速开始后，纤维腺瘤的微观外观与正常成年雌性大鼠中生长的肿瘤相似。在肿瘤生长的缓慢和加速阶段，乳腺均保持萎缩状态，其他第二性征表现也是如此。在垂体切除术后的大鼠中，雌酮和孕酮联合使用可刺激肿瘤生长，额外给予催乳素或生长激素可加速这种生长。这些激素单独使用均不能刺激肿瘤生长。在去卵巢大鼠中，乳腺和纤维腺瘤的生长还表现出其他差异。单独注射孕酮可加速肿瘤生长，但对乳腺生长无此作用。酚类雌激素对肿瘤生长有双相作用，而对宿主乳腺的作用是单相的。随着这些酚类剂量逐渐增加，首先是肿瘤生长速度加快，直至达到峰值；剂量超过最佳量后，肿瘤生长受到抑制。在这些荷瘤大鼠的乳腺中未观察到生长抑制阶段。许多能在乳腺中诱导妊娠变化的类固醇可加速肿瘤生长。其中包括联合使用的雌酮和孕酮以及单独使用的17α - 乙炔基 - 19 - 去甲睾酮。但用4 - 雄烯 - 3α,17β - 二醇处理的大鼠乳腺出现了妊娠变化，肿瘤却未生长。我们所提供的证据证明，所测试的乳腺纤维腺瘤具有正常乳腺的一些功能特性，也具有肿瘤特征。在对激素的反应方面，它具有使其有别于大鼠所有其他内分泌靶器官的特点。
