2004 Fiscal Year Final Research Report Summary
Role of NF-κB activation in hormone-refractory prostate cancer
| Project/Area Number |
15591685
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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 | Osaka University |
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Principal Investigator |
NISHIMURA Kazuo Osaka University, Graduate School of Medicine, Department of Urology, Associate Professor, 医学系研究科, 講師 (80303957)
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| Co-Investigator(Kenkyū-buntansha) |
NONOMURA Norio Osaka University, Graduate School of Medicine, Department of Urology, Associate Professor, 医学系研究科, 助教授 (30263263)
OKUYAMA Akihiko Osaka University, Graduate School of Medicine, Department of Urology, Professor, 医学系研究科, 教授 (20093388)
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| Project Period (FY) |
2003 – 2004
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| Keywords | NF-κB / RANKL / IL-6 / IL-8 / VEGF |
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| Research Abstract |
Establishment of xenograft models using prostate cancer cell lines and osteblastic cell lines
Xenograft models using LNCaP, MDA-PCa2b and LNCaP mixed with MC3T3-E1cells were established on dorsal subcutaneous lesion of nude mice.
Assessment of the expression of NF-κB, androgen receptor, and SRC-3 by immunohistochemical study
Xenograft samples and clinical prostate samples obtained from patients with hormone-naive or hormone-refractory prostate cancer were used for immunohistochemical analysis. NF-κB mainly showed cytoplasmic expression in both xenografts and any stage of clinical prostate cancer. Less than 20% of cancer cells showed nuclear NF-κB expression in these samples. Higher gleason grade tumors had higher percentage of positivity of nuclear NF-κB expression.
Expression levels of androgen receptor and SRC-3 in clinical prostate cancer were correlated.
The effect of prostate cancer on oeteoclastgenesis
Crude conditioned medium (CM) from LNCaP, DU145, PC3 and MDA PCa2b cells enhanced mRNA for receptor activator of NF-κB ligand (RANKL) in MC3T3-E1cells. However, these CM did not affect osteoprotegerin (OPG) mRNA expression in MC3T3-E1cells. CM from LNCaP, DU145 cells also enhanced maturation of osteoclast precursor cells (Cancer letter, in press).
Serum levels of IL-6, TGF-β1, IL8 and VEGF in patients with hormone-refractory prostate cancer
After disease progression, serum IL-6 levels significantly elevated, whereas serum TGF-β1 levels significantly declined. Higher serum IL-6 levels had significant association with poor prognosis, whereas higher serum TGF-β1 levels did not. After disease progression, serum IL-8 and VEGF levels increased marginally.
The effect of NF-κB inhibitor, MG132, on prostate cancer growth
A proteosomal inhibitor, MG132, inhibits the activation of NF-κB. MG132 inhibited the growth of LNCaP, DU145 and PC3 cells significantly in vitro.
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