Document Detail


Inducible expression of FGF-3 in mouse mammary gland.
MedLine Citation:
PMID:  12169667     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblast growth factor-3 (FGF-3) is a crucial developmental regulator. Aberrant activation of this gene by mouse mammary tumor virus insertion results in pregnancy-responsive mammary tumorigenesis. To characterize better FGF-3 function in postnatal mammary gland development and cancer initiation/progression, we used a mifepristone (RU486)-inducible regulatory system to express conditionally FGF-3 in the mammary epithelium of transgenic mice. Ectopic overexpression of FGF-3 in pubescent mammary glands elicited severe perturbations in early mammary gland development leading to mammary hyperplasia. Ductal elongation was retarded, multiple cysts persisted in the virgin ducts, and ductal epithelium was expanded and multilayered. The altered ductal architecture and the persistence of hyperplastic multilayered epithelium reflect a defect in growth regulation, which resulted from an imbalance between mitogenic and apoptotic signals. By altering the duration of RU486 treatment, we showed that the persistence of mitogenic signal elicited by FGF-3 is crucial for the initiation, progression, and maintenance of the hyperplastic characteristic of the mammary epithelium. The manifestations elicited by FGF-3 could be reversed by RU486 withdrawal. In addition, synergism between the stimulus from estrogen and FGF-3 mitogenic pathways was evident and likely contributes to the pregnancy-dependent tumorigenesis of FGF-3. Taken together, the mifepristone-inducible regulatory system provides a powerful means for understanding the diverse roles of FGF-3 and its interactions with hormones in mammary gland tumorigenesis.
Authors:
Elly S W Ngan; Zhi-Qing Ma; Steven S Chua; Francesco J DeMayo; Sophia Y Tsai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2002-08-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  99     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-21     Completed Date:  2002-09-27     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11187-92     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion Molecules / genetics
Disease Progression
Epithelial Cells / physiology
Female
Fibroblast Growth Factor 3
Fibroblast Growth Factors / genetics*
Gene Expression Regulation, Developmental / physiology*
Hyperplasia
Mammary Glands, Animal / drug effects,  metabolism*,  pathology
Mammary Neoplasms, Animal / genetics*,  pathology*
Mice
Mice, Transgenic
Mifepristone / pharmacology
Ovariectomy
Proto-Oncogene Proteins / genetics*
Sexual Maturation
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Fgf3 protein, mouse; 0/Fibroblast Growth Factor 3; 0/Proto-Oncogene Proteins; 62031-54-3/Fibroblast Growth Factors; 84371-65-3/Mifepristone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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