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
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