Martins Filipe Correia, Botelho Maria Filomena, Cabrita António Manuel, de Oliveira Carlos Freire
Department of Gynecology ,University Hospital of Coimbra, Portugal.
Tumori. 2010 Nov-Dec;96(6):999-1003.
The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue.
In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry.
Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway.
These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice.
微环境在乳腺癌进展中具有公认的作用。尽管存在不同理论，但早期妊娠对乳腺癌发生的保护机制尚不清楚。由于妊娠负责乳腺分化，我们检验了分化的乳腺上皮细胞可能抑制乳腺癌进展的假说。换句话说，早期妊娠的保护作用可能归因于分化程度更高的乳腺组织的抑制作用。
为了检验我们的假说，我们使用了30只雌性Balb/c裸鼠和乳腺腺癌的MCF-7细胞。雌性小鼠被分为两个试验组，即I组（GI）和II组（GII），以及一个对照组。在GII组中，动物在3周龄时接受左侧腹股沟第四乳腺的上皮清除。两组均接受持续激素治疗以模拟乳腺的妊娠发育。然后将200万个MCF-7细胞注射到第四腹股沟乳腺（GI）或相应的清除乳腺脂肪垫（GII）中。五周后处死小鼠并切除肿瘤。测定肿瘤发生率和肿瘤体积，并通过免疫组织化学评估增殖和凋亡情况。
GII组小鼠的肿瘤平均体积大于GI组小鼠（P = 0.001，Mann-Whitney U检验），且增殖明显增加，增殖细胞核抗原（PCNA）染色强度更高表明了这一点。由于肿瘤呈现半胱天冬酶8染色，细胞死亡可能涉及凋亡激活，主要通过外源性途径。
这些结果表明，分化完整的乳腺可能对小鼠乳腺肿瘤生长具有抑制作用。
