Induction of TGF-beta by an antiprogestin in the human breast cancer cell line T-47D

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Abstract

Background: Antiprogestins appear to be a new approach for the endocrine therapy of breast cancer. Most breast cancer cells are growth inhibited by TGF-beta. Any change of tumorcellular TGF-beta secretion could have some impact on tumorcellular growth. We addressed our question to whether the antiprogestin onapristone can induce TGF-beta secretion in breast cancer cells in vitro and whether a possible induction correlates with the antiproliferative effect and the receptor status of the cells. Materials and methods: We examined the ER and PR positive breast cancer cell lines MCF7 and T-47D and an ER and PR negative variant T-47D/x. Hormone receptor levels were determined by EIA, total (LTGF-beta + active TGF-beta) and active TGF-beta by a radioreceptor assay. All cell biological and antiproliferative effects were measured during basal, not estrogen-stimulated growth. Results: To our knowledge, we are the first to describe, that the TGF-beta secretion of tumor cells can be increased by an antiprogestin (total: 4.8-fold, active 2.9-fold). A stimulation was found only in the markedly PR positive T-47D cells, in which onapristone proved to have strong antiproliferative potency. In the MCF7 and T-47D/x cells onapristone showed no induction of TGF-beta. Moreover, those cells were not growth inhibited. Whereas onapristone did not influence the ER-content, it dramatically downregulated the PR-content of the T-47D and MCF7 cells (93% and 65%, respectively). Conclusions: These observations make it likely, that the antiproliferative potency of the antiprogestin onapristone is at least partly due to the ability of onapristone, to stimulate the strong growth inhibitor TGF-beta. In contrast to the antiprogestin RU 486, onapristone showed no estrogenic activity (stimulation of growth and PR), which could be a decisive advantage in the therapy of breast cancer, taking into account, that many breast carcinomas grow estrogen dependent.

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Dannecker, C., Possinger, K., & Classen, S. (1996). Induction of TGF-beta by an antiprogestin in the human breast cancer cell line T-47D. Annals of Oncology, 7(4), 391–395. https://doi.org/10.1093/oxfordjournals.annonc.a010606

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