Identification of a novel kinase over-expressing in hormone refractory prostate cancer and its possibility as a therapeutic target for prostate cancer
2007; American Association for Cancer Research; Volume: 67; Linguagem: Inglês
ISSN
1538-7445
AutoresSuyoun Chung, Hidewaki Nakagawa, Kenji Tamura, Mutsuo Furihata, Motohide Uemura, Toyomasa Katagiri, Yasutomo Nasu, Hiromi Kumon, Tsuneharu Miki, Taro Shuin, Tomoaki Fujioka, Yusuke Nakamura,
Tópico(s)Ubiquitin and proteasome pathways
ResumoAACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 5404 Despite high response rates and clinical benefits, androgen ablation therapy does not cure advanced or relapsed prostate cancer, because hormone refractory prostate cancer (HRPC) cells inevitably emerge. There are no effective treatments available for HRPCs, and identification of novel molecular targets and therapeutic approach targeting them are urgently required. We generated the genome-wide gene expression profiles of clinical HRPC cells by using cDNA microarrays combining with laser microbeam microdissection, and identified dozens of trans-activated genes specifically in HRPC cells. Among them, in this study we focused on one novel gene coding a kinase as a molecular target for HRPC. RT-PCR and Northern blot analysis validated its over-expression in HRPC cells and no expression of normal adult organs except prostate and brain. We named it as BPSK (brain-prostate-specific kinase). The antibody specific to BPSK we generated also validated its over-expression in clinical HRPCs, but not in hormone sensitive or naive prostate cancers. Knockdown of BPSK by siRNA resulted in drastic suppression of HRPC cell growth. These findings suggested that BPSK is a promising molecular target for HRPCs, and small molecules specifically inhibiting BPSK can be promising approach for HRPC therapy.
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