The goal of our research was to determine the effects of TGFβ on differentiation and growth of normal and malignant breast epithelial cells. The influence of TGFβ on differentiation was studied in a series of normal, immortalized, and oncogene-transformed human mammary epithelial cells. The expression of human milk fat globule antigen as differentiation marker was increased ten- to fifteenfold in normal cells and two to threefold in transformed cells after treatment with 200 pM TGFβ for 30 h. All cell lines except one were growth inhibited by TGFβ. Using the estrogen receptor-positive breast cancer cell lines MCF7, ZR-75-1, T-47D, and the estrogen receptor-negative lines MDA-MB-231, SK-BR-3, Hs578T, MDA-MB-468, we found that all tested cell lines except late passage (>500) MCF7 cells were growth inhibited by TGFβ1 as well as TGFβ2. The maximal inhibition was 50% in estrogen receptor-positive and 80% in estrogen receptor-negative cell lines at concentrations of 800 and 40 pM, respectively in an anchorage-independent growth assay. All tested breast cancer cell lines secreted a TGFβ-like activity, the production of which was stimulated in MCF7 cells treated with antiestrogens and which inhibited the anchorage-independent growth of MDA-MB-231 cells. These observations suggest that the malignant phenotype in breast cancer need not be coupled with resistance to effects of TGFβ on growth and differentiation. Breast cancer cells being resistant to treatment with antiestrogens are still growth inhibited by TGFβ in vitro. This may partially explain the growth inhibitory effects of antiestrogens in mixtures of estrogen receptor-positive and -negative tumour cell populations in vivo.
|Original language||English (US)|
|Number of pages||4|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - Jun 1990|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science