Epidermal Growth Factor-Like Ligands in Breast Cancer.
Abstract
Cripto-1 (Cr-1) and Amphiregulin (Ar) are two EGF-like growth factors that occur at higher levels than normal in breast cancer cells and tissues. They occur during mammary cell proliferation in normal virgin, pregnant and lactating mouse mammary glands, and in early embryo cells. To test the roles of Cr-1, we infected normal mouse mammary cells with retroviruses over-expressing Cr-1, or an antisense version, in order to inhibit the production of this polypeptide. Cr-1 stimulated proliferation and was inhibitory to differentiation (lactation). Reduction of Cr-1 did not affect differentiation but decreased growth rate and increased apoptosis. Cr-1 overexpression transforms cells but appears not to be tumorigenic. We completely inactivated the Cr-1 genes in order to produce mice that expressed no Cr-1 in mammary glands as well as in all other tissues. To this end, we inactivated Cr-1 in embryo stem (ES) cells by homologous recombination and produced Cr-1 gene-targeted mice. Studies on these Cr-1 (-/-) cells showed that ES cell differentiation to cardiac myocytes was prevented. The "knockout" animals demonstrate that Cr-1 is essential for axis formation and embryonic development. Cr-1 absence causes aberrant proliferation of mesoderm cells, loss of migratory signals and absence of heart development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA366955
Entities
People
- Eileen D. Adamson
Organizations
- Sanford Burnham Prebys Medical Discovery Institute