Document Detail


Suppression of mammary epithelial cell differentiation by the helix-loop-helix protein Id-1.
MedLine Citation:
PMID:  7760836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell proliferation and differentiation are precisely coordinated during the development and maturation of the mammary gland, and this balance invariably is disrupted during carcinogenesis. Little is known about the cell-specific transcription factors that regulate these processes in the mammary gland. The mouse mammary epithelial cell line SCp2 grows well under standard culture conditions but arrests growth, forms alveolus-like structures, and expresses beta-casein, a differentiation marker, 4 to 5 days after exposure to basement membrane and lactogenic hormones (differentiation signals). We show that this differentiation entails a marked decline in the expression of Id-1, a helix-loop-helix (HLH) protein that inactivates basic HLH transcription factors in other cell types. SCp2 cells stably transfected with an Id-1 expression vector grew more rapidly than control cells under standard conditions, but in response to differentiation signals, they arrested growth and formed three-dimensional structures similar to those of control cells. Id-1-expressing cells did not, however, express beta-casein. Moreover, 8 to 10 days after receiving differentiation signals, they lost three-dimensional organization, invaded the basement membrane, and then resumed growth. SCp2 cells expressing an Id-1 antisense vector grew more slowly than controls; in response to differentiation signals, they remained stably growth arrested and fully differentiated, as did control cells. We suggest that Id-1 renders cells refractory to differentiation signals and receptive to growth signals by inactivating one or more basic HLH proteins that coordinate growth and differentiation in the mammary epithelium.
Authors:
P Y Desprez; E Hara; M J Bissell; J Campisi
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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:  Molecular and cellular biology     Volume:  15     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-06-28     Completed Date:  1995-06-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3398-404     Citation Subset:  IM    
Affiliation:
Department of Cancer Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects*
Cell Line
DNA-Binding Proteins / metabolism,  pharmacology*
Epithelial Cells
Epithelium / drug effects
Helix-Loop-Helix Motifs*
Inhibitor of Differentiation Protein 1
Mammary Glands, Animal / drug effects*
Mice
Repressor Proteins*
Signal Transduction
Transcription Factors*
Grant Support
ID/Acronym/Agency:
AG10004/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Idb1 protein, mouse; 0/Inhibitor of Differentiation Protein 1; 0/Repressor Proteins; 0/Transcription Factors
Comments/Corrections

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