Funahashi Satomi, Okazaki Yasumasa, Nagai Hirotaka, Chew Shan Hwu, Ogawa Kumiko, Toyoda Takeshi, Cho Young-Man, Toyokuni Shinya
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Division of Pathology, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
J Toxicol Pathol. 2019 Jan;32(1):19-26. doi: 10.1293/tox.2018-0029. Epub 2018 Sep 1.
Fibroadenoma (FA) is a common mammary fibroepithelial tumor. The tumor size of the FA is increased by estrogen, progesterone, prolactin, and pregnancy, whereas it decreases after menopause. These observations in humans indicate that FA is hormone dependent. In rats, the most common mammary neoplasm is also FA. Expression levels of Twist1, a transcriptional regulator of epithelial-mesenchymal transition, were examined in paraffin-embedded tissue sections of an experimental rat breast model to find physiological alternations coincident with reproductive hormonal changes. Twenty-three Fischer 344/Brown Norway F1 hybrid rats were used as 14- to 16-week-old adolescent rats (n=3), pregnant rats (n=4), and lactating rats (n=6) in addition to rats over 100-weeks-old that exhibited aging (n=3) and FA (n=7). Seventy-six cases of chemically induced breast carcinoma and two cases of FA in Sprague Dawley rats were also examined. Using tissue sections, we observed that Twist1-positive mesenchymal cells were predominantly located in the periductal region in adolescent and pregnant rats and in the terminal duct lobular unit in pregnant and elderly rats. Twist1 was also expressed diffusely in the mesenchymal cells of FA rats. Twist1-positive cancer-associated mesenchymal cells were found more frequently in the invasive components of breast carcinomas than in intraductal components. The expressions of Twist1 in mesenchymal cells were induced by physiological and pathological stimuli, suggesting the biological role of Twist1 in tissue structure. Further study may reveal the role of Twist1 in mesenchymal cells of mammary glands in rats.
纤维腺瘤（FA）是一种常见的乳腺纤维上皮性肿瘤。FA的肿瘤大小会因雌激素、孕激素、催乳素和妊娠而增大，而在绝经后则会减小。这些在人类中的观察结果表明FA是激素依赖性的。在大鼠中，最常见的乳腺肿瘤也是FA。为了找出与生殖激素变化相一致的生理改变，我们检测了上皮-间质转化的转录调节因子Twist1在实验性大鼠乳腺模型石蜡包埋组织切片中的表达水平。使用了23只Fischer 344/布朗挪威F1杂交大鼠，其中包括14至16周龄的青春期大鼠（n = 3）、怀孕大鼠（n = 4）和哺乳期大鼠（n = 6），此外还有超过100周龄表现出衰老的大鼠（n = 3）和患有FA的大鼠（n = 7）。还检测了76例化学诱导的Sprague Dawley大鼠乳腺癌和2例FA。通过组织切片，我们观察到Twist1阳性的间充质细胞主要位于青春期和怀孕大鼠的导管周围区域以及怀孕和老年大鼠的终末导管小叶单位。Twist1在FA大鼠的间充质细胞中也呈弥漫性表达。Twist1阳性的癌症相关间充质细胞在乳腺癌的浸润成分中比在导管内成分中更常见。Twist1在间充质细胞中的表达受到生理和病理刺激的诱导，提示Twist1在组织结构中的生物学作用。进一步的研究可能会揭示Twist1在大鼠乳腺间充质细胞中的作用。
