Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer.

Abstract:

:Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors. This isoform is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. Prostate cancer cell lines and prostate tumors express more BTK-C transcript than the malignant NAMALWA B-cell line or human lymphomas. BTK protein expression is also observed in tumor tissue from prostate cancer patients. Down regulation of this protein with RNAi or inhibition with BTK-specific inhibitors, Ibrutinib, AVL-292 or CGI-1746 decrease cell survival and induce apoptosis in prostate cancer cells. Microarray results show that inhibiting BTK under these conditions increases expression of apoptosis related genes, while overexpression of BTK-C is associated with elevated expression of genes with functions related to cell adhesion, cytoskeletal structure and the extracellular matrix. These results are consistent with studies that show that BTK signaling is important for adhesion and migration of B cells and suggest that BTK-C may confer similar properties to prostate cancer cells. Since BTK-C is a survival factor for these cells, it represents both a potential biomarker and novel therapeutic target for prostate cancer.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Kokabee L,Wang X,Sevinsky CJ,Wang WL,Cheu L,Chittur SV,Karimipoor M,Tenniswood M,Conklin DS

doi

10.1080/15384047.2015.1078023

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1604-15

issue

11

eissn

1538-4047

issn

1555-8576

journal_volume

16

pub_type

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