2006 Fiscal Year Final Research Report Summary
Androgen receptor influences the invasion and metastasis in prostate cancer molecular biological study
| Project/Area Number |
17591668
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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 | University of Toyama |
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Principal Investigator |
FUSE Hideki University of Toyama, Department of Urology, Professor, 大学院医学薬学研究部, 教授 (40143292)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAKAWA Osamu University of Toyama, Department of Urology, Assistant professor, 大学院医学薬学研究部, 講師 (00217978)
AKASHI Takuya University of Toyama, Department of Urology, Instructor, 附属病院, 助教 (70345560)
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| Project Period (FY) |
2005 – 2006
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| Keywords | prostate cancer / androgen receptor / invasion / extracellular matrices / chemokine / HGF / HAI-1 / metastasis |
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| Research Abstract |
We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA.
1: Androgen receptor (AR) may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells by influencing the expression of specific integrin subunits.
2: DU-145 cells selectively expressed CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed vigorous migratory responses to its ligand CXCL12 and CCL3. In contrast, neither CXCL12 nor CCL3 affected the migration of DU-145/AR cells. These results indicate that expression of AR down-regulates the migratory responses of human prostate cancer cells via chemokine and its receptor systems.
3: CXCR4 was detected in 94% of the biopsy specimens from patients with metastatic prostate cancer. CXCR4 expression showed no association with the pathological grade, extent of bony metastasis, or clinical response to hormonal therapy. Patients with a strong expression of CXCR4 in tumors revealed poorer cause-specific survival than those with a weak expression of CXCR4. Multivariate analysis showed that CXCR4 expression and pathological grade were significant prognostic factors. The CXCR4 content assayed using immunohistochemical staining was considered to be a useful prognostic factor for patients with metastatic prostate cancer treated with androgen withdrawal therapy.
4: Prostate cancer cell and prostate epithelial cell expressed HGF activator inhibitor type1 (HAI-1), but prostate stromal cell did not. The soluble-type HAI-1 expression in the supernatant showed the same result. Androgen influenced the expression of HAI-1 in some prostate cell lines.
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