Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus
| Autor: | Hussam Y. Hariri, Sumedha Gunewardena, Imala D. Alwis, William J. Hendry, Isabel R. Hendry |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Guinea Pigs Diethylstilbestrol Uterus Uterine hyperplasia Hamster Biology Toxicology Article Andrology Pregnancy Proliferating Cell Nuclear Antigen Internal medicine medicine Animals Hyperplasia Mesocricetus Gene Expression Profiling Oncogenes Cadherins biology.organism_classification medicine.disease Gene expression profiling medicine.anatomical_structure Endocrinology Animals Newborn Receptors Androgen Dysplasia Uterine Neoplasms Insulin Receptor Substrate Proteins Female medicine.symptom medicine.drug |
| Zdroj: | Reproductive Toxicology. 50:68-86 |
| ISSN: | 0890-6238 |
| Popis: | 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. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1). |
| Databáze: | OpenAIRE |
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