| Project/Area Number |
11671562
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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 | Nagasaki University |
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Principal Investigator |
SAKAI Hideki University Hospital attached to School of Medicine, Nagasaki University Assistant Professor, 医学部・附属病院, 講師 (40235122)
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| Co-Investigator(Kenkyū-buntansha) |
井川 掌 長崎大学, 医学部, 助手 (40295069)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | prostate cancer / beta-microseminoprotein / PSP94 / aberrant mRNA / probasin / androgen deprivation / rat prostate / mouse prostate / in situ hybridization |
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| Research Abstract |
1. To clarify the significance of aberrant β-microseminoprotein (β-MSP/PSP94) gene expression in prostate cancer, we designed an oligo-DNA probe specific to aberrant β-MSP/PSP94 (PSP57) mRNA.We investigated the expression of PSP57 mRNA in prostate cancer cells (PC-3, LNCaP and DU-145) and cancerous tissues by in situ hybridization method. PSP57 mRNA expression was observed in LNCaP cells but not in prostate biopsy tissues. These results suggest that PSP57 mRNA expression may not be clinically significant.
2. We performed cDNA and genomic cloning of mouse β-MSP/PSP94 gene, and found several highly conserved characteristics of β-MSP/PSP94 among different species. We investigated the gene expression of β-MSP/PSP94 and its tissue distribution in various rodent tissues by RT-PCR and in situ hybridization. Gene expression was found only in the prostate.
3. We generated a polyclonal rabbit antibody against rat β-MSP/PSP94. We found that β-MSP/PSP94 was located primarily in rat prostate and that β-MSP/PSP94 is present at different levels in different lobes of rat prostate, with significant levels detectable only in the lateral lobe.
4. β-MSP/PSP94 expression after androgen deprivation therapy was investigated in a comparative study with PSA.β-MSP/PSP94 expression in benign prostate persists under androgen deprivation compared to PSA.β-MSP/PSP94 synthesis in high grade tumor appears to be activated in the absence of androgen stimulation, indicating the possible alternative pathways in the regulation of β-MSP/PSP94.
5. We studied the gene expression of β-MSP/PSP94 with rat probasin (rPB), a gene typically responsive
6. to androgen regulation. β-MSP/PSP94 gene expression at the transcriptional level is more specific to the dorsolateral prostate than rPB and thus less sensitive to androgen ablation. This may have clinical implications for strategies to target the prostate in cancer therapy.
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