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Identification of metastasis suppressor genes for prostate cancer and analysis of genetic changes during progression of prostate cancer methamphetamine model---

Research Project

Project/Area Number 11307029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

ICHIKAWA Tomohiko  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 講師 (20241953)

Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥27,640,000 (Direct Cost: ¥26,500,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2001: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥17,700,000 (Direct Cost: ¥17,700,000)
KeywordsProstate cancer / Tumor suppressor genes / Metastasis suppressor genes / KAI1 / Chromosome 8 / Metastasis / 遺伝子クローニング
Research Abstract

Identification of molecular and cellular markers for the metastatic ability of prostate cancer would be useful in developing diagnostic methods for substaging histologically localized prostate cancers. To isolate metastasis suppressor genes, I have established a rat prostate cancer system. In this system, I used a microcell mediated chromosome transfer technique to introduce a single copy of normal human chromosomes into highly metastatic rat prostate cancer.
In the previous studies, I isolated KAI1/CD82, a metastasis suppressor gene for prostate cancer, from 11p11.2 and demonstrated that KAI1/CD82 was down-regulated during the progression of human prostate cancer. In the present study, I demonstrate that this down regulation seems to be related to methylation.
By using the same method, I reported that another metastasis suppressor gene was located on the human chromosome region 8p21-p12. In the present study, I have isolated the 60-kb fragment from this region that contains the metastasis suppressor gene. I have also analyzed the genetic significance of this region in prostate cancer, and found that LOH of the region is associated with progression of prostate cancer.
Mitogen-activated protein kinase kinase 4 (MKK4, a metastasis suppressor gene) was identified from 17p11.2 by the method described above. In this study, I have published that MKK4 gene expression is inversely related to histological pattern in advancing human prostate cancers.
I have reviewed LOH data on prostate cancer, and found that common sites of allelic loss that are consistently observed by various methods seem to exist on chromosome arms 8p, 10q, I3q, and 16q. I have also found that chromosome arm 12p may contain tumor suppressor genes for prostate cancer.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Gao AC, et al.: "Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2"Prostate. 38(1). 46-54 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda T, et al.: "Identification of a 1-cM region of common cleletion on 13g14 associated with metastasis of human prostate cancer"Genes Chromosomes Cancer. 24(2). 183-190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Y, et al.: "Radiotherapy for local progression in patients with hormone-refractory prostate cancer"Int. J. Urol.. 6(4). 187-191 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Y, et al.: "Progonosis of patients with T4 prostate carcinoma"Int. J. Urol.. 6(4). 192-195 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akakuma K, et al.: "External beam radiation monotherapy for prostate cancer"Int. J. Urol.. 6(8). 408-413 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa T, et al.: "Mapping of metastasis suppressor genes for prostate cancer by microcell-medicated chromosome transfer"Asian J. Androl.. 2(3). 167-171 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦: "アンドロゲン受容体の遺伝子の変異"癌と化学療法. 14(7). 682-689 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦: "前立腺癌の遺伝的背景"日本泌尿器科学会卒後・生涯教育テキスト. 5(2). 137-148 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 鈴木 啓悦, 他: "前立腺癌に対する新しい腫瘍マーカーの可能性"泌尿器科. 14(臨増). 461-463 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kito H, et al.: "Hypermechylation of the CD44 gene is associated with progression and metastasis of human prostate cancer"Prostate. 49(2). 110-115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imamoto T, et al.: "Pretreatment serum level of testosterone as aprognostic factor in Japanese men with hurmonally treated stage D2 prostate cancer"Endocrine J.. 48(5). 573-578 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nihei N, et al.: "Functional evidence for a metastasis suppressor gene for rat prostate cancer within a 60 kilobase region on human chromosome 8p21-p12"Cancer Res.. 62(2). 367-370 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawana Y, et al.: "Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer"Prostate. in press. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦: "前立腺癌における転移抑制遺伝子の同定"泌尿器外科. 12(臨増). 363-364 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦: "前立腺癌の発癌機序と再燃機序癌遺伝子、癌抑制遺伝子の異常"日本臨床. 58(増刊). 41-44 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa T, et al.: "Role of chromosomal loss in the progression of prostate cancer"Int. J. Clin. Oncol.. 5(6). 345-354 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Y, et al.: "Effect of prostatic biopsy on free-to-total prostate-specific antigen ratio in patients with prostate cancer"Int. J. Urol.. 7(2). 49-53 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Y, et al.: "Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia"Int. J. Urol.. 7(6). 447-451 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim HL, et al.: "Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing"Cancer Res.. 61(7). 2833-2837 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Y, et al.: "Endcrine therapy for recurrence after definitire radio therapy in patients with prostate cancer"Int. J. Urol.. 8(5). 222-226 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekita N, et al.: "Epigenetic regulation of the KAI1 metastasis suppressor gene in human prostate cancer cell lines"Jpn. J. Cancer. Res.. 92(9). 947-951 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦, 他: "泌尿器科腫瘍学入門"日本医学館. 271 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 市川 智彦, 他: "看護のための最新医学講座 第22巻"中山書店. 394 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gao, A. C., Lou, W., Ichikawa. T., Denmeade, S. R., Barrett, J. C., Isaacs, J. T.: "Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2"Prostate. 38(1). 46-54 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda, T., Emi, M., Suzuki, H., Komiya, A., Akakura, K., Ichikawa. T., Shiraishi, T., Masai, M., Igarashi, T., Ito, H.: "Identification of a 1-cM region of common deletion on 13q14 associated with metastasis of human prostate cancer"Genes Chromosomes Cancer. 24(2). 183-193 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya, Y., Akakura, K., Akimoto, S., Ichikawa. T., Ito, H.: "Radiotherapy for local progression in patients with hormone-refractory prostate cancer"Int. J. Urol.. 6(4). 187-191 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya, Y., Akakura, K., Ichikawa. T., Ito, H.: "Prognosis of patients with T4 prostate carcinoma"Int. J. Urol.. 6(4). 192-195 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akakura, K., Furuya, Y., Suzuki, H., Kmiya, A., Ichikawa. T., Igarashi, T., Tanaka, M., Murakami, S., Ito, H.: "External beam radiation monotherapy for prostate cancer"Int. J. Urol.. 6(8). 408-413 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa, T., Hosoki, S., Suzuki, H., Akakura, K., Igarashi, T., Furuya, Y., Oshimura, M., Rinker-Schaeffer, C. W., Nihei, N., Barrett, J. C., Isaacs, J. T., Ito, H.: "Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer"Asian J. Androl.. 2(3). 167-171 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa, T., Suzuki, H., Ito, H.: "Role of chromosomal loss in the progression of prostate cancer"Int. J. Clin. Oncol.. 5(6). 345-354 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya, Y., Akakura, K., Ichikawa, T., Masai, M., Igarashi, T., Ito, H.: "Effect of prostatic biopsy on free-to-total prostate-specific antigen ratio in patients with prostate cancer"Int. J. Urol.. 7(2). 49-53 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya, Y., Akakura, K., Tobe, T., Ichikawa. T., Igarashi, T., Ito, H.: "Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia"Int. J. Urol.. 7(6). 447-451 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim, H.L., Griend, D.J., Yang, X., Benson, D.A., Dubauskas, Z., Yoshida, B.A., Chekmareva, M.A., Ichikawa, Y., Sokoloff, M.H., Zhan, P., Karrison, T., Lin, A., Stadler, W.M., Ichikawa, T., Rubin, M.A., Rinker-Schaeffer, C.W.: "Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers"Cancer Res.. 61(7). 2833-2837 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya, Y., Akakura, K., Tanaka, M., Ichikawa, T., Igarashi, T., Murakami, S., Ito, H.: "Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer"Int. J. Urol.. 8(5). 222-226 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekita, N., Suzuki, H., Ichikawa, T., Kito, H., Akakura, K., Igarashi, T., Nakayama, T., Watanabe, M., Shiraishi, T., Toyota, M., Yoshie, O., Ito, H.: "Epigenetic regulation of the KAI1 metastasis suppressor gene in human prostate cancer cell lines"Jpn. J. Cancer Res.. 92(9). 947-951 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kito, H., Suzuki, H., Ichikawa, T., Sekita, N., Kamiya, N., Akakura, K., Igarashi, T., Nakayama, T., Watanabe, M., Harigaya, K., Ito, H: "Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer"Prostate. 49(2). 110-115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imamoto, T., Suzuki, H., Akakura, K., Komiya, A., Nakamachi, H., Ichikawa, T., Igarashi, T., Ito, H.: "Pretreatment serum level of testosterone as a prognostic factor in Japanese men with hormonally treated stage D2 prostate cancer"Endocrine J.. 48(5). 573-578 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nihei, N., Kouprina, N., Larionov, V., Oshima, J., Martin, G.M., Ichikawa, T., Barrett, J.C.: "Functional evidence for a metastasis suppressor gene for rat prostate cancer within a 60-kilobase region on human chromosome 8p21-p12"Cancer Res.. 62(2). 367-370 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawana, Y., Ichikawa, T., Suzuki, H., Ueda, T., Komiya, A., Ichikawa, Y., Furuya, Y., Akakura, K., Igarashi, T., Ito, H.: "Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer"Prostate. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim HL, et al.: "Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histolugical pattern in advancing human prostatic cancers"Cancer Res.. 61・7. 2833-2837 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Furuya Y., et al.: "Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer"Int.J.Urol.. 8・5. 222-226 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sekita N., et al.: "Epigenetic regulation of the KAI1 metastasis suppressor gene in human prostate cancer cell lires"Jpn.J.Cancer.Res.. 92・9. 947-951 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kito H., et al.: "Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer"Prostate. 49・2. 110-115 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imamoto T., et al.: "Pretreatment serum level of testosterone as a prognostic factor in Japanese men with normonally treated stage D2 prostate cancer"Endo crine J.. 48・5. 573-578 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nihei N., et al.: "Functional Evidence for a metastasis suppressor gene for rat prostate cancer within 60-kilobase region on human chromosome 8p21-p12"Cancer Res.. 62・2. 367-370 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawana Y., et al.: "Loss of heterozygusity at 7q31.1 and 12p13-12 in advanced prostate cancer"Prostate. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 鈴木 啓悦, 他: "前立腺癌に対する新しいマーカーの可能性"泌尿器外科. 14・臨増. 461-463 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 市川 智彦, 他: "看護のための最新医学講座 第22巻"中山書店. 394 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ichikawa,T., et al.: "Role of chromosomal loss in the progression of prostate cancer."Int.J.Clin.Oncol. . 5(6). 345-354 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ichikawa,T., et al.: "Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome tranfer,"Asian J.Androl.. 2(3). 167-171 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furuya,Y., et al.: "Changes in serum prostate-specific antigen following prostatectomy in patients with benign postate hyperplasia."Int.J.Urol.. 7(6). 447-451 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 市川智彦: "前立腺癌の癌化と再燃のメカニズム"臨床と研究. 77(3). 18-22 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 市川智彦: "前立腺癌の発癌機序と再燃機序癌遺伝子・癌抑制遺伝子の異常"日本臨床. 58(増刊). 41-44 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 市川智彦: "アンドロゲン受容体の遺伝子の変異"Biotherapy. 14(7). 682-689 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nihei, N., et al.: "Metastasis suppressor gene(s) for rat prostate cancer on the long arm of human chromosome 7"Genes Chromosomes Cancer. 24(1). 1-8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueda, T., et al.: "Identification of a 1-cM region of common deletion on 13q14 associated with metastasis of human prostate cancer"Genes Chromosomes Cancer. 24(2). 183-190 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furuya, Y., et al.: "Radiotherapy for local progression in patients with hormone-refractroy prostate cancer"Int. J. Urol.. 6(4). 187-191 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furuya, Y., et al.: "Progression of patients with T4 prostate carcinoma"Int. J. Urol.. 6(4). 192-195 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furuya, Y., et al.: "Effect of prostatic biosy on free-to-total prostate-specific antigen ratio in patients with prostate cancer"Int. J. Urol.. 7(2). 49-53 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 市川 智彦: "前立腺癌における転移抑制遺伝子の同定."泌尿器外科. 12(臨増). 363-364 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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