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ANALYSIS OF TR3 RECEPTOR IN APOPTOSIS OF PROSTATE CANCER AND APPLICATION FOR DIAGNOSIS OF PROSTATE CANCER RECCURENCE

Research Project

Project/Area Number 08671830
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionYOKOHAMA CITY UNIVERSITY

Principal Investigator

UEMURA Hiroji  DEP.UROL., YOKOHAMA CITY UNIVERSITY, ASSIST.PROF, 医学部, 講師 (50244439)

Co-Investigator(Kenkyū-buntansha) HOSAKA Masahiko  DEP.UROL., YOKOHAMA CITY UNIVERSITY, PROF, 医学部, 教授 (30106330)
KUBOTA Yoshinobu  DEP.UROL., YOKOHAMA CITY UNIVERSITY, ASSOC.PROF, 医学部, 助教授 (10106312)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsPROSTATE CANCER / STEROID RECEPTOR / APOPTOSIS
Research Abstract

(1) A role of TR3 orphan receptor in drug-induced prostate apoptosis
In androgen-responsive LNCaP human prostatic cancer cells, human TR3 orphan receptor can be rapidly induced by stimulation of androgen or growth factors (i.e., EGF or FGF). In contrast, ablation of androgen by castration can also induce the expression of TR3 orphan receptor gene in rat ventral prostate which underwent programmed cell death (apoptosis) characterized by DNA fragmentation ladder. This phenomenon prompted us to further analyze the roles of human TR3 orphan receptor in apoptosis-induced prostate cancer cells. Northern blot analysis shows that human TR3 orphan receptor can be induced rapidly after treatment of 10 mM calcium ionophore or 300 mM etoposide (VP 16) in LNCaP cells. Antisense TR3 orphan receptor stable transfectant LNCaP cells indicated a much higher concentration of etoposide was needed to show the similar apoptosis as compared to the control (vector) stable transfectant LNCaP cells. Together, ou … More r data suggest that human TR3 orphan receptor may play an important role of drug-induced apoptosis in human prostate cancer cells.
(2) Induction of an intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFR) gene by the TR3 orphan receptor
A hormone response element, CNTER-NERB (5'-AAAGGTCA-3') has been identified in the fifth intron of the alpha component of CNTFR gene for the human TR3 orphan receptor. A specific binding between in vitro expressed TR3 and CNTFR-NBRE was demonstrated by using electrophoretic mobility shift assay. A reporter gene assay using CAT showed that CNTFR has an enhancer activity that could be induced by TR3 receptor in a dose-dependent manner. This induction was significantly reduced in the absence of CNTFR-BNBRE. Together, these results indicate CNTFR-NBRE is sufficient to mediate TR3 action in inducing the enhancer activity of CNTFR. Our finding may, therefore, suggest CNTFR is a target gene regulated by TR3 and expand the role of TR3 in the nervous system.
(3) In situ hybridization of TR3 receptor in prostate cancer tissues.
Recently, Jenkins et al. showed clear data in which c-myc amplification in prostate cancer tissues and metastatic lymphnodes was detected using fluorescence in situ hybridization. Our in situ hybridization data in human prostate cancer, benign prostate hypertrophy, and normal prostate tissues revealed that the expression patterns of TR3 orphan receptor mRNA were very similar to those of c-myc. More interestingly, TR3 orphan receptor mRNAs were more highly expressed in prostate cancer area than in adjacent normal or benign hypertrophic tissue. Furthermore, these expressions were highly seen in poorly differentiated adenocarcinoma area. These data suggest that the TR3 orphan receptor may play some important roles in development or progression of prostate cancer in the same manner as the c-myc oncogene.
(4) Telomerase activities in prostate cancer tissues.
We analyzed the telomerase activity in association with the pathological differentiation of prostate cancer. Telomerase activity was examined by PCR-based telomeric repeat amplification protocol (TRAP) assay. The results showed that most of prostate cancer tissues (90%) displayed telomerase activity and high activity in primary and biopsy specimens were more frequent detected in poorly differentiated adenocarcinoma. Also, the expression of catalytic subunit, hTERT, was detected by RT-PCR. It revealed that the expression in 70% of prostate cancer tissues was more highly seen in comparison with those in normal prostate tissues. Less

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] H.Uemura & C.Chang: "Antisense TR3 orphan receptor can in crease prostate cell viability with etopside treatment"Endocrinology. 139. 2329-2334 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] X.Mu, H.Uemura et al.: "Inducion of an intronic enhancer of the human ciliary neurotrophic factor receptor gene by the TR3 orphan receptor"Endocrine. 9. 27-32 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Lin, H.Uemura et al.: "Detection of tdomerase activity in prostate needl-biopsy 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] Y.Lin, H.Uemura et al.: "Telomerase activity in primary prostate cancer"J.of 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] Y.Lin, H.Uemura et al.: "Telomerase activity in human bladcler cancer"Clin.Cancer Research.. 2. 929-932 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Miyamoto, H.Uemura et al.: "Molecular basis of sex hormone receptor function"(Springer) H.Gomeneyer, U.Farhmann and K.Parczyk. 236 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Uemura and C. Chang: "Antisense TR3 orphan receptor can increase prostate cell viability with etoposide treatment"Endocrinology. 139,5. 2329-2334 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] X. Mu, W.J.Young, Y. Lin, H. Uemura and C. Chang: "Induction of an intronic enhancer of the human ciliary neurotrophic factor receptor gene by the TR3 orphan receptor"Endocrine. 9,1. 27-32 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y. Lin, H. Uemura, Y. Kubota and M. Hosaka: "Telomerase activity in primary prostate cancer"J. Urol.. 157,3. 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] Y. Kubota and H. Uemura et al.: "Molecular diagnosis of human prostate cancer"Jpn. J. Cancer Clin.. 42. 1661-1668 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y. Lin, H. Miyamoto, K. Fujinami, H. Uemura, M. Hosaka and Y. Kubota: "Telomerase activity in human bladder cancer"Clin. Cancer Res.. 2. 929-932 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Miyamoto, S. Yeh, C. Wang, H. Uemura and C. Chang: "The androgen receptor co-regulator, ARA70. Molecular basis of sex hormone receptor function. (edt. H. Gromeneyer, U. Farhmann and K. Parczyk)"Springer. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Uemura: "Antisense TR3 orphan receotpr cain increase prostate Cancer cell viability with etoposide treatment" Endocrinology. 139. 2329-2334 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] X,Mu.H.Uemura et al: "Induction of an intronic enhanced of the CNTFRα gene by the TR3 orphan receptor" Endocrine. 9. 27-32 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Miyamoto et al.: "Molecular Basis of Sex Hormore Receptov Function" H.Gromeneyer,U.Farhmann and K.Parczyk, 236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroji Uemura, et al.: "Suppression of apoptosis in prostage cancer LNCap cells by anti sense TR3 orphanreceptor" Endocrinology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 上村 博司, ほか: "ヒト前立腺癌組織のテロメラーゼ活性と組織分化度" 日本臨状. (印刷中). (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] 上村博司: "Key Word 1997-98 泌尿器系" (斎藤泰,小林知彦,穂坂正彦編)先端医学社, 227 (1996)

    • Related Report
      1996 Annual Research Report

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

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