3 results on '"Bouillez A"'
Search Results
2. MUC1-C drives MYC in multiple myeloma
- Author
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Maroof Alam, Donald Kufe, Audrey Bouillez, Teru Hideshima, David Avigan, Reddy Gali, Yu-Tzu Tai, Kenneth C. Anderson, Hasan Rajabi, Ashujit Tagde, and Shannon T. Bailey
- Subjects
0301 basic medicine ,Telomerase ,Transcription, Genetic ,Glutamate-Cysteine Ligase ,Immunology ,Down-Regulation ,Biology ,Response Elements ,Biochemistry ,digestive system ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D2 ,Transcription (biology) ,Cell Line, Tumor ,Gene silencing ,Humans ,skin and connective tissue diseases ,Transcription factor ,neoplasms ,beta Catenin ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Messenger RNA ,Lymphoid Neoplasia ,Mucin-1 ,Cell Biology ,Hematology ,TCF4 ,Molecular biology ,biological factors ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,CRISPR-Cas Systems ,Multiple Myeloma - Abstract
Multiple myeloma (MM) cell lines and primary tumor cells are addicted to the MYC oncoprotein for survival. Little is known, however, about how MYC expression is upregulated in MM cells. The mucin 1 C-terminal subunit (MUC1-C) is an oncogenic transmembrane protein that is aberrantly expressed in MM cell lines and primary tumor samples. The present studies demonstrate that targeting MUC1-C with silencing by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 editing or with the GO-203 inhibitor is associated with downregulation of MYC messenger RNA and protein. The results show that MUC1-C occupies the MYC promoter and thereby activates the MYC gene by a β-catenin/transcription factor 4 (TCF4)-mediated mechanism. In this way, MUC1-C (1) increases β-catenin occupancy on the MYC promoter, (2) forms a complex with β-catenin and TCF4, and, in turn, (3) drives MYC transcription. Analysis of MM cells using quantitative real-time reverse transcription polymerase chain reaction arrays further demonstrated that silencing MUC1-C is associated with downregulation of MYC target genes, including CCND2, hTERT, and GCLC Analysis of microarray data sets further demonstrated that MUC1 levels positively correlate with MYC expression in MM progression and in primary cells from over 800 MM patients. These findings collectively provide convincing evidence that MUC1-C drives MYC expression in MM.
- Published
- 2015
3. MUC1-C drives MYC in multiple myeloma.
- Author
-
Ashujit Tagde, Rajabi, Hasan, Bouillez, Audrey, Alam, Maroof, Gali, Reddy, Bailey, Shannon, Yu-Tzu Tai, Teru Hideshima, Anderson, Kenneth, Avigan, David, and Kufe, Donald
- Subjects
- *
MUCINS , *GENE silencing , *CRISPRS , *MYC proteins , *MESSENGER RNA , *CATENINS , *TRANSCRIPTION factors - Abstract
Multiple myeloma (MM) cell lines and primary tumor cells are addicted to the MYC oncoprotein for survival. Little is known, however, about how MYC expression is upregulated in MM cells. The mucin 1 C-terminal subunit (MUC1-C) is an oncogenic transmembrane protein that is aberrantly expressed in MM cell lines and primary tumor samples. The present studies demonstrate that targeting MUC1-C with silencing by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 editing or with the GO-203 inhibitor is associated with downregulation of MYC messenger RNA and protein. The results show that MUC1-C occupies the MYC promoter and thereby activates the MYC gene by a β-catenin/transcription factor 4 (TCF4)-mediated mechanism. In this way, MUC1-C(1) increases β-catenin occupancy on the MYC promoter, (2) forms a complex with β-catenin and TCF4, and, in turn, (3) drives MYC transcription. Analysis of MM cells using quantitative real-time reverse transcription polymerase chain MYC reaction arrays further demonstrated that silencing MUC1-C is associated with downregulation of MYC target genes, including, CCND2, hTERT, and GCLC. Analysis of microarray data sets further demonstrated that MUC1 levels positively correlate with MYC expression in MM progression and in primary cells from over 800 MM patients. These findings collectively provide convincing evidence that MUC1-C drives MYC expression in MM. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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