title: Neonatal diethylstilbestrol treatment alters the estrogen-regulated expression of both cell proliferation and apoptosis-related proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x) in the hamster uterus.
abstract: In the Syrian hamster, neonatal diethylstilbestrol (DES) treatment and then postpubertal estrogen stimulation induces hyperplasia plus apoptosis (preneoplastic responses) and ultimately neoplasia in the endometrial epithelial cell compartment. As part of a project to investigate the molecular and cellular mechanisms responsible for this phenomenon, expression of several proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2 and bcl-x) was compared in estrogen-stimulated uteri from control versus neonatally DES-treated hamsters. According to Northern blot analysis of total uterine RNA, levels of the 3.2-kb c-jun and 2.4-kb c-myc transcripts were not altered by neonatal DES treatment. However, the 1.0 kb bax and 2.7 kb bcl-x transcript levels were significantly increased in the neonatally DES-exposed uteri. According to immunohistochemical analysis of paraformaldehyde-fixed and paraffin-embedded tissue sections, levels of c-Jun, c-Fos, c-Myc, Bax, and Bcl-x proteins were enhanced dramatically in both the luminal and glandular epithelial cells of neonatally DES-exposed uteri. In contrast, the immunostaining signal for Bcl-2 protein was decreased consistently in the epithelial cells of neonatally DES-exposed uteri. In conclusion, neonatal DES treatment induced persistent and epithelial cell-specific imbalances in the estrogen-regulated uterine expression of c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x proto-oncogenes. These imbalances likely play a role in the molecular mechanism by which neonatal DES treatment induces altered estrogen responsiveness including hyperplasia, apoptosis, and ultimately neoplasia in the epithelial compartment of the hamster uterus.
authors.affiliation: Department of Biological Sciences, Wichita State University, Kansas 67260-0026, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: W J
authors.initials: WJ
authors.lastname: Hendry
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D017209:Apoptosis; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D008647:Mesocricetus; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D004968:Estrogens, Non-Steroidal; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004054:Diethylstilbestrol