title: Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells.
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.
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawakami
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Takanobu
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Chul Jang
authors.initials: CJ
authors.lastname: Kim
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Okada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugihara
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Reeve
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Keisei
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D016158:Genes, p53; D006801:Humans; D007713:Klinefelter Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA