title: Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus.
abstract: Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: (1) immunoblot analyses and (2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and (3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: (1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and (2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon.
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, KS 67260-0026, United States. Electronic address: william.hendry@wichita.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hendry
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, KS 67260-0026, United States.
authors.forename: Hussam Y
authors.initials: HY
authors.lastname: Hariri
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, KS 67260-0026, United States.
authors.forename: Imala D
authors.initials: ID
authors.lastname: Alwis
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States; Bioinformatics Core, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Sumedha S
authors.initials: SS
authors.lastname: Gunewardena
authors.affiliation: Department of Biological Sciences, Wichita State University, Wichita, KS 67260-0026, United States.
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Hendry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000502:physiology; D004054:Diethylstilbestrol / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D006168:Guinea Pigs; D006965:Hyperplasia; D055504:Insulin Receptor Substrate Proteins / Q000032:analysis; D008647:Mesocricetus; D009857:Oncogenes; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; D055504:Insulin Receptor Substrate Proteins; D018809:Proliferating Cell Nuclear Antigen; D011944:Receptors, Androgen; D004054:Diethylstilbestrol
keywords: Diethylstilbestrol; Endocrine disruption; Female reproductive system; Neoplasia; Uterus