Effects of tamoxifen on telomerase activity in breast carcinoma cell lines.

The authors tested the effects of the antiestrogenic agent tamoxifen on telomerase activity and cell proliferation in MCF-7 and MDA-MB-231 breast carcinoma cell lines. MCF-7 cells belong to a known estrogen receptor positive cell line, whereas MDA-MB-231 cells, previously thought to be estrogen receptor negative, are now shown to contain estrogen receptor-beta. Both cell lines were grown in the presence of tamoxifen 10(-6), 10(-7), 10(-8), and 10(-9) M for 10 days. Cells in separate flasks were harvested daily for determination of total cell number, protein was extracted for determination of telomerase activity, and RNA was extracted for reverse transcriptase-polymerase chain reaction analysis to measure expression levels of the telomerase components (the RNA component and the catalytic subunit) and estrogen receptors. Total cell counts and telomerase activity levels of both cell lines with 10(-8) M tamoxifen treatment were lower than control cells and other tamoxifen treatments. Changes in the expression of individual telomerase components correlated with telomerase activity. Estrogen receptor status did not correlate with telomerase activity. Tamoxifen strongly affected both cell count and telomerase activity within the 10(-8) M concentration of both cell lines. Cells were able to overcome drug inhibition at all other doses after 4 days. Telomerase activity and cell proliferation were correlated in both cell lines and depended on drug concentration. Tamoxifen showed long term effects on cell proliferation of the MCF-7 cells.