title: Altered microRNA expression patterns during the initiation and promotion stages of neonatal diethylstilbestrol-induced dysplasia/neoplasia in the hamster (Mesocricetus auratus) uterus.
abstract: Treatment of Syrian hamsters on the day of birth with the prototypical endocrine disruptor and synthetic estrogen, diethylstilbestrol (DES), leads to 100% occurrence of uterine hyperplasia/dysplasia in adulthood, a large proportion of which progress to neoplasia (endometrial adenocarcinoma). Consistent with our prior gene expression analyses at the mRNA and protein levels, we now report (based on microarray, real-time polymerase chain reaction, and in situ hybridization analyses) that progression of the neonatal DES-induced dysplasia/neoplasia phenomenon in the hamster uterus also includes a spectrum of microRNA expression alterations (at both the whole-organ and cell-specific level) that differ during the initiation (upregulated miR-21, 200a, 200b, 200c, 29a, 29b, 429, 141; downregulated miR-181a) and promotion (downregulated miR-133a) stages of the phenomenon. The biological processes targeted by those differentially expressed miRNAs include pathways in cancer and adherens junction, plus regulation of the cell cycle, apoptosis, and miRNA functions, all of which are consistent with our model system phenotype. These findings underscore the need for continued efforts to identify and assess both the classical genetic and the more recently recognized epigenetic mechanisms that truly drive this and other endocrine disruption phenomena.
authors.affiliation: Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS, 67260-0026, USA.|Department of Molecular and Cell Biology, The University of Texas at Dallas, Richardson, TX, 75080, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Padmanabhan
authors.affiliation: Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS, 67260-0026, USA.
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Hendry
authors.affiliation: Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Knapp
authors.affiliation: Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS, 67260-0026, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Shuai
authors.affiliation: Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS, 67260-0026, USA. william.hendry@wichita.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hendry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D008647:Mesocricetus; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D014594:Uterine Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D052244:Endocrine Disruptors; D035683:MicroRNAs; D004054:Diethylstilbestrol
keywords: Diethylstilbestrol; Endocrine disruption; Female reproductive system; MicroRNA; Neoplasia; Uterus