Document Detail

Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes.
MedLine Citation:
PMID:  11739006     Owner:  NLM     Status:  MEDLINE    
We have previously demonstrated that overexpression of parathyroid hormone-related protein (PTHrP) in the mammary glands of transgenic mice results in defects in ductal elongation and branching during puberty and in lobuloalveolar development during pregnancy. In addition, we have shown that PTHrP is necessary for the formation of the initial ductal tree during embryonic mammary development. In order to examine the effect of varying the timing of PTHrP overexpression on mammary development, we created tetracycline-regulated, K14-tTA/Tet(O)-PTHrP double transgenic mice. In this report, we document that this 'tet-off' system directs transgene expression to the mammary gland and that it is fully repressed in the presence of tetracycline. Using these mice, we demonstrate that transient overexpression of PTHrP before birth causes defects in ductal branching during puberty and that overexpression of PTHrP during puberty decreases the rate of ductal elongation. Furthermore, we demonstrate that if PTHrP overexpression is initiated after ductal morphogenesis is completed, lobuloalveolar development is unaffected. Finally, we demonstrate that the impairment in ductal elongation caused by PTHrP is associated with an increase in the basal rate of epithelial cell apoptosis in terminal end buds and a failure to increase end bud cell proliferation and decrease apoptosis in response to estrogen and progesterone.
M E Dunbar; P Dann; C W Brown; J Van Houton; B Dreyer; W P Philbrick; J J Wysolmerski
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of endocrinology     Volume:  171     ISSN:  0022-0795     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-12-12     Completed Date:  2002-01-22     Revised Date:  2010-04-12    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  403-16     Citation Subset:  IM    
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
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MeSH Terms
Apoptosis / physiology
Cell Division / physiology
Embryonic and Fetal Development / physiology
Gene Expression Regulation, Developmental
Mammary Glands, Animal / cytology,  embryology,  growth & development*
Mice, Transgenic
Morphogenesis / physiology
Parathyroid Hormone-Related Protein
Proteins / genetics,  physiology*
Grant Support
Reg. No./Substance:
0/Parathyroid Hormone-Related Protein; 0/Proteins; 60-54-8/Tetracycline

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