1998 Fiscal Year Final Research Report Summary
Study of the Identification of new genes associated with development and recurrence of prostate cancer
| Project/Area Number |
08457428
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Yokohama City University |
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Principal Investigator |
KUBOTA Yoshinobu Yokohama City Univ. School of Med., Asso. Professor, 医学部, 助教授 (10106312)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Hiroji Yokohama City Univ. School of Med., Assi. Professor, 医学部, 講師 (50244439)
HOSAKA Masahiko Yokohama City Univ. School of Med., Professor, 医学部, 教授 (30106330)
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| Project Period (FY) |
1996 – 1998
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| Keywords | prostate cancer / Telomerase / defferential display / liprin-α2 |
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| Research Abstract |
Prostate cancer is one of the most common neoplasms in the Western country. Molecular background of this disease is still unclear. Thus, We studied the expression of telomerase gene in prostate cancer as one of new genes and also, We applied differential display PCR (DD-PCR) to identify androgen-regulated and prostate cancer specific genes in prostate cancer.
1) Telomerase activity was analyzed in prostate cancer tissyues and biopsy samples using PCR based TRAP assay. As a results, expression of telomerase gene was consistent among the cancer of prostate. And detecting telomerase activity in biopsy sample could be useful as a diagnostic marker for prostate ccncer.
2) The RNA of LNCaP cells treated with dihydrotestosterone (DHT), and RNA from cancer tissues and normal prostate tissues from same patients were analyzed for differentially expressed genes. Using DD-PCR, we identified down regulated and up-regulated cDNA fragment by DHT in LNCaP cells. And also c-DNA specifically expressed in cancer tissues were identified. These fragments were then sequenced.
Sequence analysis revealed that a cDNA fragment as one of interesting genes is identical to protein tyrosine phosphatase LAR related gene, liprin -α2. Liprin -α2 was downregulated by dihydrotestosterone (DHT) in LNCaP cells in a time- and androgen concentration-dependent manner. This gene was not expressed in androgen independent prostate cell lines PC-3 and DU-145 at the mRNA level. We have also identified NKX 3.1 like gene, OSM-beta and other genes as prostate cancer asoociated genes in this research.
These data suggest that liprin-α2 is directly regulated by androgens and the loss of this gene expression might be associated with progression of prostate cancer to androgen independence. Further analysis are on going for clarify the function of other genes identified in prostate cancer.
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[Publications] Lin,Y., Uemura,H., Fujinami,K., Hosaka,M., Harada,M., Kubota,Y.: "Telomerase activity in primary prostate cancer"Journal of Urology. 157. 1161-1165 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Orikasa,K., Fukushige,S., Hoshi,S., Orikasa,S., Kondo,K., Miyoshi,Y., Kubota,Y., Horii,A.: "Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer"J Hum Genet. 43. 228-230 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Murata,M., Shiraishi,T., Fukutome,K., Watanabe,M., Nagao,M., Kubota,Y., Ito,H., Kawamura,J., Yatani,R.: "Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan"Jpn J Clin Oncol. 28(11). 657-660 (1998)
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[Publications] Lin,Y., Uemura,H., Fujinami,K., Hosaka,M., Iwasaki,Y., Kitamura,H., Harada,M., Kubota,Y.: "Detection of telomerase activity in prostate needle-biopsy samples"Prostate. 36. 121-128 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Masuda,M., Iki,M., Noguchi,S., Mikata,K., Kubota,Y., Harada,M., Hosaka,M.: "The worst histologic elements predict prognosis in moderately-differentiated prostate cancer patients with androgen-withdrawal endocrine therapy"Eur Urol. 36. 197-202 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyoshi,Y., Uemura,H., Fujinami,K., Mikata,K., Harada,M., Kitamula,H., Koizumi,Y., Kubota,Y.: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in japanese patients"Prosatate. (in press).
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「研究成果報告書概要(欧文)」より
