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Understanding mammary gland development through the imbalanced expression of growth regulators
Author(s) -
Robinson Gertraud W.,
Smith Gilbert H.,
Gallahan Daniel,
Zimmer Andreas,
Furth Priscilla A.,
Hennighausen Lothar
Publication year - 1996
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199606)206:2<159::aid-aja5>3.0.co;2-h
Subject(s) - biology , transgene , mammary gland , transforming growth factor , cellular differentiation , microbiology and biotechnology , genetically modified mouse , gene expression , gene , genetics , cancer , breast cancer
Functional differentiation of mammary tissue progresses in distinct phases spanning puberty and pregnancy. Here we have analyzed and compared the effects of transforming growth factor β1 (TGFβ1), TGFα, and whey acidic protein (WAP), the Notch‐related cell fate protein Int3, and p53 and pRb on mammary development. We chose transgene expression from the WAP gene promoter which is only active in mammary alveolar cells. The imbalanced expression of these molecules specifically altered development and differentiation of the gland. While TGFα did not disturb alveolar outgrowth, little or no alveolar structures developed in the presence of Int3. TGFβ1, WAP, and the expression of SV40 T‐antigen—which inactivates p53 and pRb—reduced overall alveolar development. The expression of individual milk protein genes was affected differentially by the transgenes. A WAP‐lacZ transgene served as an additional indicator of terminal differentiation of alveolar cells. Homogeneous expression of lacZ was seen in mice transgenic for lacZ, or for TGFα and lacZ. In contrast, only a few differentiated cells were observed in the presence of TGFβ1 and Tag. Thus, the expression of growth regulators in the same defined subset of mammary cells results in distinct developmental changes and a specific pattern of alveolar differentiation. © 1996 Wiley‐Liss, Inc.