title: Gene expression profile of terminal end buds in rat mammary glands exposed to diethylstilbestrol in neonatal period.
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.
authors.affiliation: Department of Molecular and Cellular Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. umekita@m2.kufm.kagoshima-u.ac.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Umekita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Souda
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Taiji
authors.initials: T
authors.lastname: Hamada
authors.forename: Takako
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens; D002364:Caseins / Q000096:biosynthesis; D004054:Diethylstilbestrol / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005836:Genitalia, Female / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D046228:Microarray Analysis; D042282:Microdissection; D008894:Milk Proteins / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002273:Carcinogens; D002364:Caseins; D004968:Estrogens, Non-Steroidal; D008894:Milk Proteins; D016328:NF-kappa B; C024471:whey acidic proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D012313:RNA; D004054:Diethylstilbestrol