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Study of the Identification of new genes associated with development and recurrence of prostate cancer

Research Project

Project/Area Number 08457428
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionYokohama City University

Principal Investigator

KUBOTA Yoshinobu  Yokohama City Univ. School of Med., Asso. Professor, 医学部, 助教授 (10106312)

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)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywordsprostate cancer / Telomerase / defferential display / liprin-α2 / 男性ホルモン依存性 / 遺伝子 / 再燃 / Differential Display
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.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kubota Y. et al: "Do the worst histological elements in needlebiopsy specimens of prostate cancer predict prognosis"Lancet. 348. 822-823 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lin Y. et al: "Telomemse activity in primary prostate cancer"J.Urology. 157. 1161-1165 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orikasa.K. et al: "Infrequent geneticaltemtions of PTEN gene in japanese patients with sporadic prostate cancer"J.Hum.Genet. 43. 228-230 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lin Y. et al: "Detection of telomerase activity in prostate needlebiopsy samples"Prostate. 36. 121-128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuda M et al: "The worst histologic elements predict prognosis in modemtdy differentiated prostate cancer patients with androgen-* therapy"Eur Urol. 36. 197-207 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyoshi Y. et al: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies prostate cancer in japanese"Prostate. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 窪田吉信: "Molecular Medicine : 遺伝子病マニュアル(下) 癌遺伝子・癌抑制遺伝子関連異常 : 前立腺癌"中山書店. 2 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isaacs,J.T.et al: "First International Consultation on prostate cancer (WHO-UICC)"Growth kegulation of normal and maligned prostate cells. 50 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubota,Y., Kondo,I., Harada,M., Noguchi,S., Hosaka,M.: "Do the worst histlogical elements in needle biopsy specimens of prostate cancer predict prognosis?"Lancet. 348. 822-823 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ln Y.,Uemura,H.Hsaka,M.Kubota.Y.: "Detection of telomernce activity in prostate needle biopsysample" Prostate. 36. 121-128 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Noguchi.S.,Shuin,T.Kubota Y.et al: "High alkaline phosphalate activity in 3P-induced human renal cauce,cells" Cancer letters. 131. 223-227 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大内秀紀・窪田吉信: "泌尿器科悪性腫瘍の遺伝子治療" 腎と臨床. 44. 774-778 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 窪田 吉信: "前立腺癌の治療-遺伝子治療の進歩" 病理と臨床. 16. 1411-1418 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lim.Y.et.al.: "Telomerase activity in primary prostate cance" Journal of Urology. 157. 1161-1165 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Lim.Y.et.al.: "Detection of telomemseactivity in prostate needle bopsy samples" Prostate. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Lin.Y.et al: "Telomerase activity in primary prostate cancer" J.Urology. 157. 1161-1165 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kubota.Y.et al: "Do the worschistological elements in needle biopsyspocimens of prostate cancer predict prognost?" Lancet. 348. 822-823 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyamoto.H.et al: "Bilateral adrenocortical carlinoma showing loss of Heterogygosity at P53 and RB gene loci" Cancer Genetico Cytogenetics. 88. 181-183 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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