Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1.

Journal Article

The transforming growth factors beta (TGFs-beta) are potent inhibitors of cell proliferation and are usually secreted in a latent form. TGF-beta 1, TGF-beta 2, and TGF-beta 3 are expressed in distinct but overlapping patterns in the developing mouse mammary gland. To study the role of transforming growth factor-beta 1 (TGF-beta 1) in normal mammary development and in mammary neoplasia, we have constructed three transgenic mouse lines that express a simian TGF-beta 1 s223/225 mutated to produce a constitutively active product under the control of the MMTV enhancer/promoter. Expression of the transgene, as confirmed by in situ hybridization, immunohistochemistry, and Northern blot analysis, was associated with marked suppression of the normal pattern of mammary ductal tree development in female transgenics. Reduction in total ductal tree volume was observed at 7 weeks, soon after estrous begins, and was most apparent at 13 weeks, as ductal growth in the normal mammary gland declines. This effect was seen in all three lines. However, during pregnancy, alveolar outgrowths developed from the hypoplastic ductal tree, and lactation occurred, therefore, all transgenic females could feed full litters. Unlike many other transgenic mouse models in which expression of growth factors or oncogenes under control of the MMTV promoter leads to mammary epithelial hyperplasia and increased tumor formation, the MMTV-TGF-beta 1S223/225 transgene causes conditional hypoplasia of the mammary ductal tree and no spontaneous tumors have been detected in the MMTV-TGF-beta 1S223/225 transgenic animals.

Full Text

Duke Authors

Cited Authors

  • Pierce, DF; Johnson, MD; Matsui, Y; Robinson, SD; Gold, LI; Purchio, AF; Daniel, CW; Hogan, BL; Moses, HL

Published Date

  • December 1993

Published In

Volume / Issue

  • 7 / 12A

Start / End Page

  • 2308 - 2317

PubMed ID

  • 8253379

International Standard Serial Number (ISSN)

  • 0890-9369

Language

  • eng

Conference Location

  • United States