Functional Analysis of Steroid hormone orphan receptor in hormone refractory prostate cancer

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: UEMURA Hiroji Yokohama City University School of Medicine, Department of Urology, Assistant Professor, 医学部, 講師 (50244439)
• Co-Investigator(Kenkyū-buntansha): KUBOTA Yoshinobu Yokohama City University School of Medicine, Department of Urology, Professor, 医学部, 教授 (10106312) ; HOSAKA Masahiko Yokohama City University School of Medicine, Department of Urology, Professor (30106330)
• Project Period (FY): 1999 – 2001
• Keywords: Steroid hormone orphan receptor / prostate cancer / transcription factor

Research Abstract

Prostate specific antigen (PSA) has been widely recognized as a most reliable tumor marker. A recent report of immunohistochemistry has demonstrated the inverse correlation between PSA staining intensity and tumor grade in prostate cancer tissues. The molecular mechanism of this phenomenon has been as yet unknown. We elucidated that a nuclear orphan receptor, COUP-TFI and TR3 receptor, had key roles in the PSA expression of prostate cancer tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that TR3 stable transfectant of LNCaP prostate cancer cells expressed low PSA despite of stimulation of androgen. Also, COUP-TFI and TR3 receptor was expressed in human prostate cancer tissues and tended to diminish coincident with decreased PSA expression. Transient transfection analyses of PSA promoter showed that COUP-TFI or TR3 receptor repressed PSA transcription in a dose-dependent manner. In situ hybridization showed that TR3 mRNA more highly expressed in high-grade prostate cancer tissues. These findings suggest that highly expression of COUP-TFI or TR3 receptor might be attributed to decrease PSA intensity in high-grade prostate cancer tissue through suppressing the PSA transcription.

Research Products

• [Publications] K.Kondo et al.: "PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinoma and renal carcinoma cell lines"International Journal of Cancer. 91. 219-224 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Y.Miyoshi, H.Uemura et al.: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification"Prostate. 4. 225-232 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] J.Ohta et al.: "Fluorescence in situ Hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies"Clinical Cancer Research. 7. 2463-2467 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Fukutome, M.Watanabe, T.Shiraishi, M.Murata, H.Uemura, Y.Kubota, J.Kawamura, H.Ito, R.Yatani.: "N-acetyltransferase 1 genetic polymorphism influences the risk of prostate cancer treatment"Cancer Letter. 136:1. 83-87 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] N.Kawano, Y.Inayama, Y.Nagashima, Y.Myagi, H.Uemura, K.Saitoh, Y.Kubota, M.Hosaka, Y.Tanaka, Y.Nakatani.: "Desmoplastic small round-cell tumor of the paratesticular region : report of an adult case with demonstration of EWS and WT1 gene fusion using paraffin-embedded tissue"Modern Pathology. 12:7. 729-734 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K.Kondo, M.Yao, K.Kobayashi, S.Ota, S.Kaneko, M.Baba, N.Sakai, T.Kishida, S.Kawakami, H.Uemura, Y.Nagasima, Y.Nakatani, M.Hosaka: "PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinoma and renal carcinoma cell lines"Int J Cancer. 91:2. 219-224 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K.Noguchi, H.Uemura, T.Miura, M.Moriyama, H.Fukuoka, K.Kitami, M.Hosaka.: "Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist"Int J Clin Oncol. 6:1. 29-33 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S.Noguchi, Y.Kubota, I.Kondoh, M.Harada, M.Masuda, H.Uemura, M.Hosaka.: "Pathologic 'fused gland' as a prognostic factor for prostate cancer"Urology Internationale. 65:2. 84-88 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Y.Miyoshi, H.Uemura, K.Fujinami, K.Mikata, M.Harada, H.Kitamura, Y.Koizumi, Y.Kubota.: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients"Prostate. 4:3. 225-232 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] J.Ohta, Y.Miyoshi, H.Uemura, K.Fujinami, K.Mikata, M.Hosaka, Y.Tokita, Y.Kubota.: "Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer"Clin Cancer Res. 7:8. 2463-2467 (2001)
  • Description: 「研究成果報告書概要(欧文)」より