1. Gene expression profile of terminal end buds in rat mammary glands exposed to diethylstilbestrol in neonatal period.
- Author
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Umekita Y, Souda M, Hatanaka K, Hamada T, Yoshioka T, Kawaguchi H, and Tanimoto A
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Animals, Newborn, Carcinogens, Caseins biosynthesis, Female, Fluorescent Antibody Technique, Gene Expression Profiling, Genitalia, Female drug effects, Mammary Neoplasms, Experimental metabolism, Microarray Analysis, Microdissection, Milk Proteins biosynthesis, NF-kappa B biosynthesis, NF-kappa B genetics, Pregnancy, RNA biosynthesis, RNA isolation & purification, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Diethylstilbestrol toxicity, Estrogens, Non-Steroidal toxicity, Gene Expression drug effects, Mammary Glands, Animal drug effects, Mammary Glands, Animal metabolism
- Abstract
Diethlstilbestrol (DES) is a synthetic estrogen prescribed to several millions of pregnant women worldwide. The risk for breast cancer after age 40 in women prenatally exposed to DES has been reported; however, the precise mechanism of susceptibility to breast cancer remains to be resolved. We investigated the global gene expression profile of terminal end buds (TEBs), the target of carcinogen, in rat mammary glands neonatally exposed to a low- or high-dose DES at postnatal days (PND) 35 and 45, equivalent to the peripubertal stage in humans. In all groups, the number of TEBs gradually increased, peaked at PND35 and decreased at PND49. At PND35 and 49, the low-dose DES-treated group (low-DES group) showed the highest number of TEBs. In the low-DES group at PND35, β-casein, γ-casein and whey acidic protein (WAP) mRNA expression increased 8.2-fold, 26.1-fold and 13.3-fold, respectively, whereas γ-casein and WAP mRNA decreased 17.6-fold and 27.7-fold, respectively, at PND49. The most significant network revealed by Ingenuity Pathway Analysis (IPA) software showed the relevance of NF-κB in low-DES group. The present findings suggest that the deregulation of mammary gland differentiation and development-related genes could be induced and cause the increased number of terminal duct lobular units (TDLUs) in human mammary glands of DES daughters in a critical period of mammary gland development., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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