2012 Fiscal Year Final Research Report
Androgen receptor mutation in androgen-independent prostate cancer
| Project/Area Number |
23659761
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MATSUMOTO Takahiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (70447374)
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| Project Period (FY) |
2011 – 2012
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| Keywords | アンドロロジー |
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| Research Abstract |
Prostate cancer development is associated with hyperactive androgen signaling. However, the molecular link between androgen receptor (AR) function and humoral factors remains elusive. A prostate cancer mouse model was generated by selectively mutating the AR threonine 877 into alanine in proatatic epithelial cells through Cre-ERT2-mediated targeted somatic mutagenesis. Such AR point mutant mice (ARpe-T877A/Y) developed hypertrophic prostates with responses to both an androgen antagonist and estrogen, although no prostatic tumor was seen. In prostate cancer model transgenic mice, the onset of prostatic tumorigenesis as well as tumor growth was significantly potentiated by introduction of the AR T877A mutation into the prostate. Genetic screening of mice identified Wnt-5a as an activator. Enhanced Wnt-5a expression was detected in the malignant prostate cancers of patients, whereas in benigh prostatic hyperplasia such aberrant up-regulation was not obvious. These findings suggest that a noncanonical Wnt signal stimulates development of prostatic tumors with AR hyperfunction.
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[Journal Article] Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer2011
Author(s)
Takahashi S., Watanabe T., Okada M., Inoue K., Ueda T., Takada I., Watabe T., Yamamoto Y., Fukuda T., Nakamura T., Akimoto C., Fujimura T., Hoshino M., Imai Y., Metzger D., Miyazono K., Minami Y., Chambon P., Kitamura T., Matsumoto T.,Kato S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108
Pages: 4938-4943
DOI
Peer Reviewed
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[Journal Article] Essential roles of androgen signaling in wolffian duct stabilization and epididymal cell differentiation2011
Author(s)
Murashima A, Miyagawa S, Ogino Y, Nishida-Fukuda H, Araki K, Matsumoto T, Kaneko T, Yoshinaga K, Yamamura K, Kurita T, Kato S, Moon AM and Yamada G.
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Journal Title
Endocrinology
Volume: 152
Pages: 1640-1651
DOI
Peer Reviewed
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