Study of the identification of new genes inducing hormone refractory prostate cancer

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11470339
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University Grant-in Aid for Scientific Research (B)(2)
• Principal Investigator: KUBOTA Yoshinobu Yokohama City Univ., School of Medicine, Professor, 医学部, 教授 (10106312)
• Co-Investigator(Kenkyū-buntansha): YAO Masahiro Yokohama City Univ., School of Medicine, Associate Professor, 医学部, 助教授 (00260787) ; UEMURA Hiroji Yokohama City Univ., School of Medicine, Associate Professor, 医学部, 講師 (50244439)
• Project Period (FY): 1999 – 2001
• Keywords: Prostate cancer / Hormone Refractory / Differential Display / OSM-? gene / nmt55 gene / Liprin? gene

Research Abstract

In this research, new human genes associated with hormone refractory prostate cancer were tried to be identified by applying differential display PCR methodology. The RNA of human Prostate cancer and normal prostate tissue was analyzed for differentially expressed gene. We have clones more than one hundred possible genes. And OSM-? and nmt55 genes were identified as important genes.
OSM-β gene is one of the tyrosine kinase type receptor family genes. This gene was shown to be highly expressed in hormone refractory prostate cancer and suggested to be involves in androgen independent growth characteristics.
The nmt55 gene is coded as one of the transcriptional factors. We have shown that the expression of this gene was closely associated with the expression of androgen receptor. This gene was shown to be disappear last in hormone refractory prostate cancer and suggested to be associated with androgen independent growth regulation.
We have also analyzed the RNA of LNCaP human prostate cancer cells treated with dihydrotestosterone for differentially expressed gene. Two important genes Liprin?-2 and NKx 3.1 like gene were cloned.
Liprinα-2 gene expression was shown to be down-regulated by androgen and this gene might be associated with the induction of apoptosis after androgen deprivation. Since Liprinα-2 gene expression disappeared completely lost in androgen independent prostate cancer cell line (PC-3, DU-145) or hormone refractory prostate cancer tissues, this gene is suggested to play a roll in the induction of hormone independent prostate cells.

Research Products

• [Publications] Miyoshi Y et al.: "Expression of AR associated protein 55 (ARA55), and androgen receptor in prostate cancer"Prostate. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishiguro H et al.: "55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with androgen receptor"Int. J. Cancer. 105(1). 26-32 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mikata K et al.: "Inhibition of Growth of Human Prostate Cancer Xenograft by Transfection of p53 gene : Gene Transfer by Electroporation"Molecular Cancer Therapeutics. 1. 247-252 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fujinami K et al.: "Liprin-α2 gene, protein tyrosine phosphate LAR interacting prostein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"Int. J. of Mol Med. 10. 173-176 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fujiwara H et al.: "Association of common missense changes in ELAC2(HPC2) with prostate cancer in a Japanese case-control series"J. Hum Genet. 47. (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Miyoshi Y et al.: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients"The Prostate. 43. 225-232 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishiguro H, Uemura H, Fujinami K, Ikeda N, Ohta S, Kubota Y: "55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with androgen receptor"Int. J. Cancer. 105(1). 26-32 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujinami K, Uemura H, Ishiguro H, Kubota Y: "Liprin? 2 gene, protein tyrosine phosphate LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"Int. J. of Mol Med. 10. 173-176 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujiwara H, Emi M, Nagai H, Nishimura T, Konishi N, Kubota Y, Ichikawa T, Takahashi S, Shuin T, Habuchi T, Ogawa O, Inoue K, Skolnick H. M, Swensen J, Camp J. N, Tavtigian V. S: "Association of common missense changes in ELAC2(HPC2) with prostate cancer in a Japanese case-control series."J. Hum. Genet. 47. (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyoshi Y, Ishiguro H, Uemura H, Fujinami K, Miyamoto H, Miyoshi Y, Kitamura H, Kubota Y: "Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer."Prostate. in press
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mikata K, Uemura H, Ohuchi H, Ohta S, Nagashima Y, Kubota Y: "Inhibition of Growth of Human Prostate Cancer Xenograft by Transfection of p53 gene: Gene Transfer by Electroporation"Molecular Cancer Therapeutics, 1. 247-252 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyoshi Y, Uemura H, Fujinami K, Mikata K, Harada M, Kitamura 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."The Prostate, 43. 225-232 (2000)
  • Description: 「研究成果報告書概要(欧文)」より