Parodi Daniela A, Greenfield Morgan, Evans Claire, Chichura Anna, Alpaugh Alexandra, Williams James, Cyrus Kedra C, Martin Mary Beth
Departments of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA.
Department of Oncology, Georgetown University, Washington, DC 20007, USA.
Int J Mol Sci. 2017 Sep 9;18(9):1939. doi: 10.3390/ijms18091939.
Environmental exposure to estrogens and estrogen like contaminants during early development is thought to contribute to the risk of developing breast cancer primarily due to an early onset of puberty; however, exposure during key developing windows may also influence the risk of developing the disease. The goal of this study was to ask whether exposure to the metalloestrogen cadmium alters mammary gland development due to acceleration of puberty onset or to an effect on early development of the mammary gland. The results show that, in addition to advancing the onset of puberty, exposure to the metalloestrogen cadmium altered mammary gland development prior to its effect on puberty onset. exposure resulted in an expansion of the number of mammosphere-forming cells in the neonatal mammary gland and an increase in branching, epithelial cells, and density in the prepubertal mammary gland. In the postpubertal mammary gland, there was a further expansion of the mammary stem/progenitor cell population and overexpression of estrogen receptor-alpha (ERα) that was due to the overexpression and altered regulation of the ERα transcripts derived from exons O and OT in response to estradiol. These results suggest that exposure to cadmium increases stem/progenitor cells, cell density, and expression of estrogen receptor-alpha that may contribute to the risk of developing breast cancer.
在早期发育过程中，环境暴露于雌激素及类似雌激素的污染物被认为主要是由于青春期提前开始，从而增加患乳腺癌的风险；然而，在关键发育窗口期的暴露也可能影响患该疾病的风险。本研究的目的是探究暴露于金属雌激素镉是否会因青春期提前开始或对乳腺早期发育的影响而改变乳腺发育。结果表明，除了提前青春期开始外，暴露于金属雌激素镉在其对青春期开始产生影响之前就改变了乳腺发育。暴露导致新生乳腺中形成乳腺球的细胞数量增加，青春期前乳腺的分支、上皮细胞和密度增加。在青春期后乳腺中，乳腺干/祖细胞群体进一步扩大，雌激素受体α（ERα）过度表达，这是由于外显子O和OT来源的ERα转录本在雌二醇作用下过度表达且调控改变所致。这些结果表明，暴露于镉会增加干/祖细胞、细胞密度以及雌激素受体α的表达，这可能会增加患乳腺癌的风险。
