title: 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.
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.|b Department of Molecular Medicine ; Pasteur Institute of Iran; Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Kokabee
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sevinsky
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Wei Lin Winnie
authors.initials: WL
authors.lastname: Wang
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Cheu
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Sridar V
authors.initials: SV
authors.lastname: Chittur
authors.affiliation: b Department of Molecular Medicine ; Pasteur Institute of Iran; Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Karimipoor
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Tenniswood
authors.affiliation: a Cancer Research Center and Department of Biomedical Sciences ; State University of New York; University at Albany ; Rensselaer , NY USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Conklin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D010880:Piperidines; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D007527:Isoenzymes; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine
keywords: BTK inhibitors; apoptosis; biomarker; cell survival; prostate cancer