LIGAND-INDEPENDENT ACTIVATION OF THE ANDROGEN RECEPTOR OF PROSTATE CANCER
| Project/Area Number |
14571483
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
UEDA Takeshi CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, 医学部附属病院, 講師 (10223463)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | prostate cancer / interleukin-6 / androgen receptor / hormone refractory status / bone metastasis / p53 / dexametasone / neuron specific enolase / 転移 / シグナル伝達経路 / 共通欠失領域 / コファクター |
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| Research Abstract |
Since the growth of prostate cancer is androgen-sensitive, metastatic disease has been treated by androgen withdrawal therapy. Most prostate cancer patients initially respond to hormonal therapy, but over half of them gradually develop resistance. The mechanism of the change in tumours from being androgen-responsive to androgen-unresponsive is generally explained by clonal selection, adaptation, an alternative pathway of signal transduction and AR involvement. The AR is highly amplified in 30% of patients with hormone-refractory prostate cancer that has been treated by castration without antiandrogens. The AR N-terminal domain in the LNCaP model is activated by IL6 via mitogen-activated protein kinase (MAPK) and single transducers and activators of transcription 3 (STAT3).
The following results are already published;
p53-Abs might be helpful in the clinical decision to perform prostate biopsy. The serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.
The pretreatment serum level of NSE can predict survival of metastatic prostate cancer patients treated with endocrine therapy.
Stage M1 patients with paraplegia had survival rates as good as stage M1 patients without paralysis. This should encourage an aggressive treatment approach. However, for patients with hormone-independent disease there seems to be no effective treatment and prognosis is poor.
Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease.
Several co-factors between AR and transcriptional complex have been cloned and reports indicate that SRC1 is correlated with the hormone-refractory progression of prostate cancer.
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Report
(3 results)
Research Products
(25 results)
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[Publications] Suzuki H, Akakura K, Komiya A, Ueda T, Imamoto T, Furuya Y, Ichikawa T, Watanabe M, Shiraishi T, Ito, H.: "CAG polymorphic repeat lengths in androgen receptor gene among Japanese prostate cancer patients : potential predictor of prognosis after endocrine therapy."Prostate. 51. 219-224 (2002)
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「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Hosoki S, Ichikawa T, Ota S, Ichikawa Y, Suzuki H, Ueda T, Naya Y, Akakura K, Igarashi T, Oshimura M, Nihei N, Barrett JC, Ito H.: "Suppression of metastasis of rat prostate cancer by introduction of human chromosome 13."Asian J Androl. 4. 131-136 (2002)
Description
「研究成果報告書概要(欧文)」より
Related Report
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