Abstract
The increased risk of several types of cancer in Klinefelter syndrome (47XXY) suggests that the extra X chromosome may be involved in the tumorigenesis associated with this syndrome. Here, we show that cancer cells (PSK-1) derived from a patient with Klinefelter syndrome (47XXY) showing loss of an inactive X chromosome subsequently gained active X chromosomes. We found that this abnormal X chromosome composition in PSK-1 is caused by a loss of an inactive X chromosome followed by multiplication of identical active X chromosomes, not by reactivation of an inactive X chromosome. Furthermore, we extended the characterization of loss-of-inactive X in a series of 22 female-derived cancer cell lines (eight breast cancer cell lines, seven ovarian cancer cell lines, and seven cervical cancer cell lines). The data demonstrate that loss-of-inactive X in the female-derived cancer cells is mainly achieved by loss of an inactive X chromosomes followed by multiplication of an identical active X chromosomes. However, distinctive pathways, including reactivation of an inactive X chromosome, are also involved in the mechanisms for loss-of-inactive X and gain-of-active X in female-derived cancer cells. The biological significance of the loss-of-inactive X and gain-of-active X in the oncogenesis of Klinefelter syndrome and female-derived cancer cells are discussed.
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Acknowledgements
We thank Masashi Suzaki for helping us with bisulfite genomic sequencing and microsatellite analysis. This work was supported in part by Grants-in-aid (13470332, 15591680, and 15591682) from the Ministry of Education, Science and Culture, Japan as well as research grants from Shimadzu Science Foundation, Uehara Memorial Foundation, and Yamanouchi Foundation for Research on Metabolic Disorders.
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Kawakami, T., Zhang, C., Taniguchi, T. et al. Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells. Oncogene 23, 6163–6169 (2004). https://doi.org/10.1038/sj.onc.1207808
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DOI: https://doi.org/10.1038/sj.onc.1207808
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