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Open AccessArticle

Alteration of Mammary Gland Development and Gene Expression by In Utero Exposure to Cadmium

1
Departments of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA
2
Department of Oncology, Georgetown University, Washington, DC 20007, USA
3
Lombardi Comprehensive Cancer Center, Research Building, 3970 Reservoir Road NW, Washington, DC 20007, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(9), 1939; https://doi.org/10.3390/ijms18091939
Received: 15 July 2017 / Revised: 1 September 2017 / Accepted: 5 September 2017 / Published: 9 September 2017
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals)
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 in utero 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, in utero exposure to the metalloestrogen cadmium altered mammary gland development prior to its effect on puberty onset. In utero 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 in utero 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. View Full-Text
Keywords: cadmium; estradiol; in utero; mammosphere-forming cells; estrogen receptor-α cadmium; estradiol; in utero; mammosphere-forming cells; estrogen receptor-α
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MDPI and ACS Style

Parodi, D.A.; Greenfield, M.; Evans, C.; Chichura, A.; Alpaugh, A.; Williams, J.; Cyrus, K.C.; Martin, M.B. Alteration of Mammary Gland Development and Gene Expression by In Utero Exposure to Cadmium. Int. J. Mol. Sci. 2017, 18, 1939.

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