Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells.
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.
Kawakami
Takahiro
T
Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Zhang
Cheng
C
Taniguchi
Takanobu
T
Kim
Chul Jang
CJ
Okada
Yusaku
Y
Sugihara
Hiroyuki
H
Hattori
Takanori
T
Reeve
Anthony E
AE
Ogawa
Osamu
O
Okamoto
Keisei
K
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
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA