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Classen, S. ; Possinger, K.W. ; Pelka-Fleischer, R.* ; Wilmanns, W.

Effect of onapristone and medroxyprogesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells.

J. Steroid Biochem. Mol. Biol. 45, 315-319 (1993)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
We studied the influence of the antiprogestin onapristone (ZK 98.299) and the progestin medroxyprogesterone acetate (MPA) on the proliferation and hormone receptor levels of the following human breast cancer cell lines: the oestrogen receptor (ER) and progesterone receptor (PR) negative cell line MDA-MB-231 and the ER- and PR-positive cell lines T47-D and SK-BR-3. MPA and onapristone both bind to the cellular PR and can inhibit the proliferation of hormone-dependent cells; PR-negative MDA-MB-231 cells are not inhibited. The growth inhibition of the ER- and PR-positive tumour cells induced by onapristone is accompanied by a significant accumulation of cells in the G0/G1 phase and a reduction of S-phase cells, while MPA does not change the distribution of the cell cycle phases. However, MPA reduces the cellular ER content by 27% and the PR content by more than 80%. Conversely, onapristone does not significantly affect ER and PR levels. The extent of growth inhibition by both drugs differs considerably: onapristone inhibits growth of both receptor positive cell lines (T47-D:39%; SK-BR-3:17%), while MPA affected growth in only SK-BR-3 (61%). These results indicate that even though the two drugs act through the PR, the inhibitory effect on the three cell lines of MPA may depend on ER concentration and its down-regulation, while the inhibitory effect of onapristone is mainly correlated to the PR concentration without significantly affecting ER levels. Since tumour cells with low ER concentration are growth suppressed by onapristone, but not by MPA, it remains to be examined whether antiprogestins should preferably be used in PR-positive tumours with a low ER concentration.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0960-0760
e-ISSN 0960-0760
Zeitschrift Journal of Steroid Biochemistry and Molecular Biology, The
Quellenangaben Band: 45, Heft: 4, Seiten: 315-319 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institut für Experimentelle Hämatologie