IGF-2 is a mediator of prolactin-induced morphogenesis in the breast.

Details

Serval ID
serval:BIB_460BA13D68A6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IGF-2 is a mediator of prolactin-induced morphogenesis in the breast.
Journal
Developmental Cell
Author(s)
Brisken C., Ayyannan A., Nguyen C., Heineman A., Reinhardt F., Tan J., Dey S.K., Dotto G.P., Weinberg R.A., Jan T.
ISSN
1534-5807 (Print)
ISSN-L
1534-5807
Publication state
Published
Issued date
2002
Volume
3
Number
6
Pages
877-887
Language
english
Abstract
The mechanisms by which prolactin controls proliferation of mammary epithelial cells (MECs) and morphogenesis of the breast epithelium are poorly understood. We show that cyclin D1(-/-) MECs fail to proliferate in response to prolactin and identify IGF-2 as a downstream target of prolactin signaling that lies upstream of cyclin D1 transcription. Ectopic IGF-2 expression restores alveologenesis in prolactin receptor(-/-) epithelium. Alveologenesis is retarded in IGF-2-deficient MECs. IGF-2 and prolactin receptor mRNAs colocalize in the mammary epithelium. Prolactin induces IGF-2 mRNA and IGF-2 induces cyclin D1 protein in primary MECs. Thus, IGF-2 is a mediator of prolactin-induced alveologenesis; prolactin, IGF-2, and cyclin D1, all of which are overexpressed in breast cancers, are components of a developmental pathway in the mammary gland.
Keywords
Animals, Breast Neoplasms/genetics, Carcinoma/genetics, Carrier Proteins, Cell Division/genetics, Cells, Cultured, Cyclin D1/deficiency, Cyclin D1/genetics, Epithelial Cells/cytology, Epithelial Cells/drug effects, Female, Gene Expression Regulation, Developmental/genetics, Genes/drug effects, Genes/genetics, Genetic Testing, Insulin-Like Growth Factor II/genetics, Insulin-Like Growth Factor II/metabolism, Mammary Glands, Animal/cytology, Mammary Glands, Animal/embryology, Membrane Glycoproteins, Mice, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Progesterone/metabolism, Progesterone/pharmacology, Prolactin/genetics, Prolactin/metabolism, RANK Ligand, RNA, Messenger/genetics, RNA, Messenger/metabolism, Receptor Activator of Nuclear Factor-kappa B, Receptors, Progesterone/deficiency, Receptors, Progesterone/genetics, Signal Transduction/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:58
Last modification date
09/11/2021 6:40
Usage data