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Steroid Hormones Induce HMG1 Overexpression and Sensitize Breast Cancer Cells to Cisplatin and Carboplatin
Qing He, Cynthia H. Liang and Stephen J. Lippard
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 11 (May 23, 2000), pp. 5768-5772
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/122531
Page Count: 5
You can always find the topics here!Topics: Cell lines, Estrogens, Hormones, HeLa cells, DNA, Epithelial cells, Adducts, Sensitization, Steroid hormones, Cell growth
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Cisplatin is an anticancer drug that has enjoyed remarkable success against testicular tumors, but dose limiting side-effects have limited its application against a broader range of cancers. Previous studies have shown that high-mobility group (HMG) domain proteins such as HMG1 sensitize cells to cisplatin by shielding its major DNA adducts from nucleotide excision repair. Estrogen treatment increases HMG1 mRNA levels in breast cancer MCF-7 cells. Herein, we describe that treatment of human cancer cells having steroid hormone receptors with the appropriate hormone, estrogen and/or progesterone, significantly increases the potency of cisplatin and its analogue carboplatin by causing the overexpression of HMG1. These findings suggest that the proper combination of these drugs, which are already approved by the Food and Drug Administration, could have potential benefit in treating tumors such as ovarian or breast that carry the hormone receptors.
Proceedings of the National Academy of Sciences of the United States of America © 2000 National Academy of Sciences