Suppression of mammary epithelial cell differentiation by the helix-loop-helix protein Id-1
- Lawrence Berkeley Lab., CA (United States); and others
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). The authors 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 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. The authors 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. 53 refs., 6 figs.
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 258954
- Journal Information:
- Molecular and Cellular Biology, Journal Name: Molecular and Cellular Biology Journal Issue: 6 Vol. 15; ISSN 0270-7306; ISSN MCEBD4
- Country of Publication:
- United States
- Language:
- English
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