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

被引：141

作者：

Brisken, C ^{[1
]}

Ayyannan, A

Nguyen, C

Heineman, A

机构：

[1] Harvard Univ, Sch Med, Dept Surg Oncol, Boston, MA 02114 USA

[2] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA

[3] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[4] Massachusetts Gen Hosp, Charlestown, MA 02129 USA

[5] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA

来源：

DEVELOPMENTAL CELL | 2002年 / 3卷 / 06期

关键词：

D O I：

10.1016/S1534-5807(02)00365-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：877 / 887

页数：11

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