YY1 modulates taxane response in epithelial ovarian cancer

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The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed ... continued below

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Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi et al. October 10, 2008.

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The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility and proliferation, but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.

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  • Journal Name: Molecular Cancer Research

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  • Report No.: LBNL-2217E
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 965885
  • Archival Resource Key: ark:/67531/metadc926641

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Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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  • October 10, 2008

Added to The UNT Digital Library

  • Nov. 13, 2016, 7:26 p.m.

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  • Nov. 18, 2016, 4:02 p.m.

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Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi et al. YY1 modulates taxane response in epithelial ovarian cancer, article, October 10, 2008; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc926641/: accessed April 27, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.