Eifert, C., Wang, X., Kokabee, L., Kourtidis, A., Jain, R., Gerdes, M. J., Conklin, D. S.
(October 2013)
A novel isoform of the B cell tyrosine kinase BTK protects breast cancer cells from apoptosis.
Genes Chromosomes and Cancer, 52 (10).
pp. 961-975.
ISSN 10452257
Abstract
Tyrosine kinases orchestrate key cellular signaling pathways and their dysregulation is often associated with cellular transformation. Several recent cases in which inhibitors of tyrosine kinases have been successfully used as anticancer agents have underscored the importance of this class of proteins in the development of targeted cancer therapies. We have carried out a large-scale loss-of-function analysis of the human tyrosine kinases using RNA interference to identify novel survival factors for breast cancer cells. In addition to kinases with known roles in breast and other cancers, we identified several kinases that were previously unknown to be required for breast cancer cell survival. The most surprising of these was the cytosolic, nonreceptor tyrosine kinase, Bruton's tyrosine kinase (BTK), which has been extensively studied in B cell development. Down regulation of this protein with RNAi or inhibition with pharmacological inhibitors causes apoptosis; overexpression inhibits apoptosis induced by Doxorubicin in breast cancer cells. Our results surprisingly show that BTK is expressed in several breast cancer cell lines and tumors. The predominant form of BTK found in tumor cells is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. This alternate form of BTK is expressed at significantly higher levels in tumorigenic breast cells than in normal breast cells. Since this protein is a survival factor for these cells, it represents both a potential marker and novel therapeutic target for breast cancer. © 2013 Wiley Periodicals, Inc.
| Item Type: |
Paper
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| Subjects: |
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Powers lab |
| Depositing User: |
Matt Covey
|
| Date: |
October 2013 |
| Date Deposited: |
20 Sep 2013 13:36 |
| Last Modified: |
19 Jul 2021 13:39 |
| PMCID: |
PMC5006942 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/28582 |
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