Nandi S, Guzman R C, Yang J
Cancer Research Laboratory, University of California, Berkeley 94720, USA.
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3650-7. doi: 10.1073/pnas.92.9.3650.
An attempt has been made to put forward a unifying hypothesis explaining the role hormones play in the genesis of mammary cancers of different phenotypes and genotypes in mice, rats, and humans. Most mammary cancers in these species originate in luminal mammary epithelial cells lining the mammary ducts and alveoli. These cancers are histopathologically diverse and are classified on the basis of growth requirements as hormone-dependent or hormone-independent tumors. In most strains of mice, mammary cancers at the time of detection are largely of the hormone-independent type; in rats, almost all mammary cancers are hormone-dependent, while humans have both phenotypes. In spite of these differences, in vivo studies show that hormones (ovarian and pituitary) are essential for luminal mammary epithelial cell proliferation and also for the development of mammary cancers of both hormone-independent and hormone-dependent types. This article, based on our extensive in vivo and in vivo studies and on current literature, proposes a model to explain the central role of hormones in the genesis of all types of mammary cancers. The model attempts to address the following questions: (i) how hormones regulate luminal mammary epithelial cell proliferation, (ii) why hormones are required for the genesis of mammary cancers of all phenotypes and genotypes, including those which are always classified as hormone-independent tumors, and (iii) why the three species (mouse, rat, and human) have consistently different ratios of hormone-dependent to hormone-independent tumors.
人们试图提出一个统一的假说，以解释激素在小鼠、大鼠和人类不同表型和基因型乳腺癌发生过程中所起的作用。这些物种中的大多数乳腺癌起源于乳腺导管和腺泡内衬的腔面乳腺上皮细胞。这些癌症在组织病理学上具有多样性，并根据生长需求分为激素依赖性或激素非依赖性肿瘤。在大多数小鼠品系中，检测时的乳腺癌大多为激素非依赖性类型；在大鼠中，几乎所有乳腺癌都是激素依赖性的，而人类则具有这两种表型。尽管存在这些差异，但体内研究表明，激素（卵巢和垂体激素）对于腔面乳腺上皮细胞增殖以及激素非依赖性和激素依赖性乳腺癌的发生都是必不可少的。本文基于我们广泛的体内和体外研究以及当前文献，提出了一个模型来解释激素在所有类型乳腺癌发生中的核心作用。该模型试图解决以下问题：（i）激素如何调节腔面乳腺上皮细胞增殖，（ii）为什么激素对于所有表型和基因型乳腺癌的发生都是必需的，包括那些一直被归类为激素非依赖性肿瘤的癌症，以及（iii）为什么这三个物种（小鼠、大鼠和人类）激素依赖性肿瘤与激素非依赖性肿瘤的比例始终不同。
