Relationship of XIST expression and responses of ovarian cancer to chemotherapy.
Relationship of XIST expression and responses of ovarian cancer to chemotherapy.
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发表时间：
2002-08
影响因子：
5.7
通讯作者：
Kuan-Chun Huang;P. Rao;C. Lau;E. Heard;S. Ng;Carolyn Brown;S. Mok;R. Berkowitz;S. Ng
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文献类型：
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作者：
Kuan-Chun Huang;P. Rao;C. Lau;E. Heard;S. Ng;Carolyn Brown;S. Mok;R. Berkowitz;S. Ng
用于表征癌症药理学的表达谱已成为发现预后标志物和癌症治疗的新分子靶标的新方法。在一项比较同一患者原发性卵巢肿瘤和复发性卵巢肿瘤之间整体 RNA 表达谱的研究中，我们发现 XIST（失活 X 染色体特异性转录本）是在复发性肿瘤中下调的差异最大的表达基因。 XIST 编码剪接的非编码多腺苷酸化转录物，其独特之处在于仅从失活的 X 染色体表达，并参与 X 失活过程。随后对一组女性癌细胞系中 XIST 表达的表征表明，XIST 的表达水平与紫杉醇敏感性显着相关。在接受紫杉醇治疗的 21 例卵巢癌病例中，XIST RNA 水平与卵巢癌患者的无病期之间的密切相关性证明了这一观察结果的临床相关性。对卵巢癌细胞系的细胞遗传学研究表明，失活 X 染色体的丢失是细胞系中 XIST 转录本丢失的机制之一。我们的数据表明 XIST 表达可能是卵巢癌化疗反应的潜在标志物。
Expression profiling to characterize cancer pharmacology has become a new approach to discover novel molecular targets for prognostic markers and cancer therapy. In a study to compare the global RNA expression profiles between primary and recurrent ovarian tumors from the same patient, we have identified XIST (inactive X chromosome-specific transcripts) as the most differentially expressed gene that was down-regulated in the recurrent tumor. XIST encodes a spliced noncoding polyadenylated transcript that is unique in being expressed exclusively from the inactive X chromosome and is involved in the X-inactivation process. Subsequent characterization of XIST expression in a panel of female cancer cell lines showed that the expression level of XIST correlates significantly with Taxol sensitivity. The clinical relevance of this observation is demonstrated by the strong association between XIST RNA levels and disease-free periods of ovarian cancer patients in a group of 21 ovarian cancer cases with Taxol in the therapeutic regiments. Cytogenetic studies on ovarian cancer cell lines indicated that loss of inactive X chromosome is one mechanism for the loss of XIST transcripts in the cell lines. Our data suggest that XIST expression may be a potential marker for chemotherapeutic responses in ovarian cancer.