Document Detail

Abnormal cell differentiation and p21 expression of endometrial epithelial cells following developmental exposure to diethylstilbestrol (DES).
MedLine Citation:
PMID:  10805141     Owner:  NLM     Status:  MEDLINE    
Gene expression relevant to abnormal cell differentiation and altered cell cycle in endometrial epithelial cells was investigated immunohistochemically in developing mouse uteri exposed neonatally to diethylstilbestrol (DES). Female CD-1 mice were given daily s.c. injections of 2 microg of DES in corn oil or were given corn oil alone (control) at 1-5 days of age and euthanatized at 5, 6, 7, 8, 15, and 22 days of age. The endometrial epithelial cells of DES-treated mice at 5-8 days of age showed enhanced staining intensity for the estrogen receptor alpha (ER alpha), whereas the stromal cells showed decreased staining reaction; the epithelial cells showed that the protein encoded by the c-fos proto-oncogene, which plays a key role in regulating diverse estrogen-related cellular differentiation patterns, was enhanced. These cells also showed increased expression of lactoferrin, a sensitive protein marker of estrogen exposure, although the staining intensity decreased after exposure ended. The stain for p21 protein, a mitotic inhibitor which suppresses cyclin-dependent kinase activity, showed frequent positively stained cells in DES-treated mice at 5-15 days of age, whereas no accumulation of p53 protein of either wild or mutant type was detected immunohistochemically in these cells. These results indicate that suppressed cell cycle activity of endometrial epithelial cells and abnormal estrogen-related differentiation at the developmental stage following neonatal DES exposure may be caused, in part, by transient altered expression of ER alpha and expression of the p21 gene, which appears to be induced by a p53-independent mechanism.
A Yoshida; R R Newbold; D Dixon
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicologic pathology     Volume:  28     ISSN:  0192-6233     ISO Abbreviation:  Toxicol Pathol     Publication Date:    2000 Mar-Apr
Date Detail:
Created Date:  2000-07-26     Completed Date:  2000-07-26     Revised Date:  2009-07-01    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  237-45     Citation Subset:  IM    
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Animals, Newborn
Cell Differentiation / drug effects
Diethylstilbestrol / toxicity*
Endometrium / drug effects*,  metabolism,  pathology
Epithelial Cells / drug effects,  metabolism,  pathology
Estrogen Receptor alpha
Estrogens, Non-Steroidal / toxicity*
Injections, Subcutaneous
Oncogene Protein p21(ras) / metabolism*
Proto-Oncogene Proteins c-fos / metabolism
Receptors, Estrogen / metabolism
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Estrogens, Non-Steroidal; 0/Lactoferrin; 0/Proto-Oncogene Proteins c-fos; 0/Receptors, Estrogen; 56-53-1/Diethylstilbestrol; EC Protein p21(ras)

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