Induction of DNA damage, inhibition of DNA synthesis, and suppression of c-myc expression by the topoisomerase I inhibitor, camptothecin, in MCF-7 human breast tumor cells.
Induction of DNA damage, inhibition of DNA synthesis, and suppression of c-myc expression by the topoisomerase I inhibitor, camptothecin, in MCF-7 human breast tumor cells.
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DOI：
10.1016/s0006-2952(97)00618-7
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发表时间：
1998-04
影响因子：
5.8
通讯作者：
P. Jain;F. Fornari;J. Randolph;M. S. Orr;D. Gewirtz
中科院分区：
文献类型：
--
作者：
P. Jain;F. Fornari;J. Randolph;M. S. Orr;D. Gewirtz
Previous work from this laboratory has demonstrated an association between the suppression of c-myc expression and the antiproliferative activity of both topoisomerase II inhibitors and ionizing radiation in MCF-7 breast tumor cells. These findings suggested that suppression of c-myc expression could be related to the induction of DNA damage in this cell line. The present studies were designed to determine whether the inhibition of topoisomerase I (and the consequent induction of DNA strand breaks) would also result in the suppression of c-myc expression. At camptothecin concentrations of 1 μM and below, there was no detectable damage (single- or double-strand breaks) in bulk DNA or suppression of c-myc expression. At camptothecin concentrations of 5, 10, and 25 μM, where suppression of c-myc expression was observed, strand breaks in bulk DNA were also detected. These findings are consistent with the idea that suppression of c-myc expression could be a component of the DNA damage response pathway in MCF-7 breast tumor cells. In contrast to the absence of detectable damage to bulk DNA or suppression of c-myc expression at the lower concentrations of camptothecin, DNA synthesis was inhibited over the entire range of drug concentrations and demonstrated a strong correspondence with growth inhibition. These observations support the concept that growth inhibition of MCF-7 cells by camptothecin is closely related to the early suppression of DNA synthesis.
