Relationship of XIST expression and responses of ovarian cancer to chemotherapy.
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.
Huang
Kuan-Chun
KC
Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rao
Pulivarthi H
PH
Lau
Ching C
CC
Heard
Edith
E
Ng
Shu-Kay
SK
Brown
Carolyn
C
Mok
Samuel C
SC
Berkowitz
Ross S
RS
Ng
Shu-Wing
SW
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D020223:Chromosome Painting; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020128:Inhibitory Concentration 50; D016014:Linear Models; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D026723:Polyadenylation; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D018076:DNA, Complementary; D005819:Genetic Markers; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D012313:RNA; D017239:Paclitaxel