Article: article from journal or magazin.
IGF-2 is a mediator of prolactin-induced morphogenesis in the breast.
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.
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
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