Tan Kah Poh, Chen Jianmin, Ward Wendy E, Thompson Lilian U
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto 150 College Street, Toronto, Ontario M5S 3E2, Canada.
Exp Biol Med (Maywood). 2004 Feb;229(2):147-57. doi: 10.1177/153537020422900203.
The exposure of rats to 10% flaxseed (FS) or an equivalent level of its major lignan, secoisolariciresinol diglucoside (SDG), during suckling enhances mammary gland differentiation, which protects against mammary carcinogenesis at adulthood. We determined whether this diet-induced mammary gland differentiation is mediated through the estrogenic pathway via epidermal growth factor receptor (EGFR) and estrogen receptor (ER) signaling. Rats were fed the AIN-93G basal diet (BD) from day 7 of pregnancy until delivery and then randomized to consume BD, FS, or SDG during lactation. After weaning, female offspring were fed BD throughout the experiment. At postnatal day (PND) 21 and the proestrus phase on PND 49-51, mammary glands of offspring were analyzed for morphology, cell proliferation, and expression of EGFR, epidermal growth factor (EGF), transforming growth factor-alpha, ER-alpha, and ER-beta. At PND 21, compared with the BD control, the number of terminal end buds (TEBs) and terminal ducts were increased by FS, whereas mammary epithelial cell proliferation was increased by both FS and SDG, suggesting that mammary morphogenesis was enhanced. Epithelial EGFR and stromal fibroblast EGF were increased by SDG, whereas epithelial ER-beta was decreased by FS. Conversely, at PND 49-51, a lower number of TEBs but a higher ratio of lobules to TEBs with decreased expression of EGFR or EGF was observed in both treatment groups. EGFR expression was positively associated with EGF expression and cell proliferation in TEB epithelium at PND 21. Urinary lignans of lactating dams were related to their offspring's indices of mammary gland development. In conclusion, exposure to FS or SDG during suckling enhanced mammary gland morphogenesis by modulation of EGFR and ER signaling, which led to more differentiated mammary glands at PND 49-51. The physiological outcomes of FS and SDG were similar, which suggests that SDG is partly responsible for the mammary gland differentiation effect.
在哺乳期将大鼠暴露于10%的亚麻籽（FS）或同等水平的其主要木脂素——开环异落叶松脂素二葡萄糖苷（SDG）中，可增强乳腺分化，从而在成年期预防乳腺癌发生。我们确定这种饮食诱导的乳腺分化是否通过表皮生长因子受体（EGFR）和雌激素受体（ER）信号传导的雌激素途径介导。从怀孕第7天到分娩，给大鼠喂食AIN-93G基础饮食（BD），然后在哺乳期随机分为食用BD、FS或SDG。断奶后，雌性后代在整个实验过程中喂食BD。在出生后第21天（PND 21）以及PND 49 - 51的动情前期，分析后代乳腺的形态、细胞增殖以及EGFR、表皮生长因子（EGF）、转化生长因子-α、ER-α和ER-β的表达。在PND 21时，与BD对照组相比，FS增加了末端终芽（TEB）和末端导管的数量，而FS和SDG均增加了乳腺上皮细胞增殖，表明乳腺形态发生增强。SDG增加了上皮EGFR和基质成纤维细胞EGF，而FS降低了上皮ER-β。相反，在PND 49 - 51时，两个治疗组均观察到TEB数量减少，但小叶与TEB的比例更高，且EGFR或EGF表达降低。在PND 21时，EGFR表达与TEB上皮中的EGF表达和细胞增殖呈正相关。哺乳期母鼠的尿木脂素与其后代的乳腺发育指标相关。总之，哺乳期暴露于FS或SDG可通过调节EGFR和ER信号传导增强乳腺形态发生，这导致在PND 49 - 51时乳腺更加分化。FS和SDG的生理结果相似，这表明SDG部分负责乳腺分化效应。
