Differences in morphology and cytoskeleton of MCF-7 and MX-1 cells after therapy with OH-tamoxifen and the pure estrogen antagonist ZM 182780. An immunofluorescence and scanning electron microscopic study.
The adjuvant endocrine therapy of breast cancer with non-steroidal antiestrogens of the triphenylethylene-type such as tamoxifen is clinically well established, and pure steroidal antiestrogens are being introduced in clinical trials to circumvent the probable occurrence of tamoxifen resistance. Nevertheless, there do still remain some unsolved questions about the exact mechanisms of these substances. We therefore investigated the different effects of 4-OH-Tamoxifen (OHT), a non-steroidal antiestrogen, versus ZM 182780, a pure steroidal antiestrogen, on the morphology and on the cytoskeleton of MCF-7 (estrogen receptor-positive) and MX-1 (estrogen receptor-negative) cells. For this purpose cells were treated for 2, 5 and 7 days with OHT, ZM182780 and different concentrations of beta-estradiol. Interestingly, in scanning electron microscopy, MCF-7 cells showed more differentiation by forming three-dimensional structures such as acini or tubule-like structures under ZM 182780 therapy than with OHT. As expected, MX-1 cells showed no effects after ZM 182780-therapy, but OHT led to a decrease in the number of these cells and produced a fibroblast-like appearance of the estrogen receptor-negative MX-1 cells. The following immunocytochemical experiments on the tubulin, vimentin, cytokeratin and actin cytoskeleton surprisingly did not show marked differences within the morphologically differentiated ZM 182780-treated population compared to the control group of MCF-7 cells. Only the OHT-treated cells of both, the ER(+) and the ER(-) cells, showed a rearrangement of actin filaments and cytokeratin which appeared even more pronounced within the ER(-) MX-1 cells. No experimental group showed morphologically detectable changes in tubulin or vimentin distribution. These data suggest a non ER-mediated OHT-effect on the cytoskeleton that also affects the ER(-) cell line MX-1.
Ehlers
E M
EM
Department of Anatomy, Medizinische Universität zu Lübeck.
Schubert
C
C
D000199:Actins / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008855:Microscopy, Electron, Scanning; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
D000199:Actins; D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D014404:Tubulin; D014746:Vimentin; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol; D007633:Keratins