Mechanistic analysis for androgen independent growth of prostate cancers

• Project/Area Number: 17590356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya City University
• Principal Investigator: ASAMOTO Makoto Nagoya City University, Graduate School of Medical Science, Associate Professor (50212494)
• Co-Investigator(Kenkyū-buntansha): 外岩戸 尚美 名古屋市立大学, 大学院医学研究科, 研究員 (70381853)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,610,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: Prostate cancer / cell culture / androgen / steroid hormone / cancer stem cells / 前立腺がん / 細胞株 / ラット / CD133 / GSTP / siRNA / 前立腺 / がん / トランスジェニック動物 / ヌードマウス / 可移植腫瘍 / マイクロアレイ

Research Abstract

We generated a transgenic rat with the SV40 T antigen under probasin promoter control, allowing prostate-specific gene expressions. Males demonstrate atypical epithelial cell proliferation in the prostate from 4 weeks of age and develop prostate carcinomas at 100% incidence before they are 15 weeks old. From the transgenic rat of 55 week-old, we established a transplanted tumor in nude mice with castration treatments. And then, we have tried to established cell lines from the nude mice tumor. Finally we established 3 cell lines. One cell line designated PCai-1 shows charcoal treated FBS insensitive growth, and two other cell lines PCai-2 and PCai-3 are sensitive for the charcoal treatment FBS with stopping growth. Characteristic gene expression profiles have been obtained for each 3 cell lines. These cell lines may be useful to study mechanisms of progression of prostate cancers, and to study chemo-prevention of prostate cancers. Furthermore, we established new cell lines from the non-castrated androgen dependent transplanted tumors. These cells had the stem cell like characters such as asymmetric tumor growth and CD133 expression.

Research Products

• [Journal Article] Glutathione S-transferase pi mediates proliferation of androgen independent prostate cancer cells (2008)
  • Author(s): Hokaiwado, N
  • Journal Title: Carcinogenesis (Epub ahead of print)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Glutathione S-transferase pi mediates proliferation of androgen independent prostate cancer cells (2008)
  • Author(s): Hokaiwado, N., Takeshita, F., Naiki-Ito, A., Asamoto, M., Ochiya, T., Shirai, T
  • Journal Title: Carcinogenesis., Epub ahead of print
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Glutathione S-transferase pi mediates proliferation of androgen independent prostate cancer cells. (2008)
  • Author(s): Hokaiwado, N.
  • Journal Title: Carcinogenesis (in press)
  • Peer Reviewed
• [Journal Article] Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate(TRAP) and human prostate carcinoma cells (2007)
  • Author(s): Tang, M
  • Journal Title: Cancer Sci 98 Pages: 471-477
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells (2007)
  • Author(s): Tang, M., Ogawa, K., Asamoto, M., Hokaiwado, N., Azman, S., Suzuki, S., Takahashi, S., Tanaka, T., Ichikawa, K., Shirai, T
  • Journal Title: Cancer Sc 98 Pages: 471-477
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate(TRAP) and human prostate carcinoma cells. (2007)
  • Author(s): Tang, M.
  • Journal Title: Cancer Sci. 98 Pages: 471-477
• [Journal Article] Characterization and application of polycolonal antibodies that specifically recog-nize JC virus large T antigen (2006)
  • Author(s): Sumden, Y
  • Journal Title: Acta.Neuropathol 111 Pages: 379-387
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin,a luteinizing hormone-releasing hormone agonist (2006)
  • Author(s): Ssid, M
  • Journal Title: Cancer Sci 97 Pages: 459-467
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Limitede effects of disrupted Gap Junctions in the liver on multi-organ carcinogenesis induced by Diisopropanolnitrosamine in the mutant Connexin 32 Transgenic rat (2006)
  • Author(s): Murasaki, T
  • Journal Title: J Toxicol Pathol 19 Pages: 93-97
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Closerelation of Transforming Growth Factor-α positive hepatic foci to hepatocel-lular tumor development in the rat (2006)
  • Author(s): Tamano, S
  • Journal Title: J Toxicol Pathol 19 Pages: 96-106
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prediction of carcinogeni cpotential by a toxicogenomic approach using rat hepato-ma cells (2006)
  • Author(s): Tsujimura, K
  • Journal Title: Cancer Sci 97 Pages: 1002-1010
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Characterization and application of polycolonal antibodies that specifically recognize JC virus large T antigen (2006)
  • Author(s): Sunden, Y., Suzuki, T., Orba, Y., Umemura, T., Asamoto, M., Nagashima, K., Tanaka, S., Sawa, H
  • Journal Title: Acta. Neuropathol 111 Pages: 379-387
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone-releasing hormone agonist (2006)
  • Author(s): Said, M., Hokaiwado, N., Tang, M., Ogawa, K., Suzuki, S., Ghanem, H. N., Esmat, A. Y., Asamoto, M., Fawzia, M. R., Shirai, T
  • Journal Title: Cancer Sci 97 Pages: 459-467
  • NAID: 10018176080
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Limited effects of disrupted Gap Junctions in the liver on multi-organ carcinogenesis induced by Diisopropanolnitrosamine in the mutant Connexin 32 Transgenic rat (2006)
  • Author(s): Murasaki, T., Asamoto, M., Hokaiwado, N., Ogawa, K., Shirai, T
  • Journal Title: J Toxicol Pathol 19 Pages: 93-97
  • NAID: 130000065694
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Close relation of Transforming Growth Factor a positive hepatic foci to hepatocellular tumor development in the rat (2006)
  • Author(s): Tamano, S., Kawabe, M., Ichihara, T., Hagiwara, A, Sano, M., Asamoto, M., Shirai, T
  • Journal Title: J Toxicol Pathol 19 Pages: 99-106
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of carcinogenic potential by a toxicogenomic approach using rat hepatoma cells (2006)
  • Author(s): Tsujimura, K., Asamoto, M., Shugo, S., Hokaiwado, N., Ogawa, K., Shirai, T
  • Journal Title: Cancer Sci 97 Pages: 1002-1010
  • NAID: 10019377814
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization and application of polycolonal antibodies that specifically recognize JC virus large T antigen. (2006)
  • Author(s): Sunden, Y
  • Journal Title: Acta. Neuropathol. 111 Pages: 379-387
• [Journal Article] Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone-releasing hormone agonist. (2006)
  • Author(s): Said, M.
  • Journal Title: Cancer Sci. 97 Pages: 459-467
• [Journal Article] Limited effects of disrupted Gap Junctions in the liver on multi-organ carcinogenesis induced by Diisopropanolnitrosamine in the mutant Connexin 32 Transgenic rat. (2006)
  • Author(s): Murasaki, T.
  • Journal Title: J Toxicol Pathol. 19 Pages: 93-97
• [Journal Article] Close relation of Transforming Growth Factor-α positive hepatic foci to hepatocellular tumor development in the rat. (2006)
  • Author(s): Tamano, S.
  • Journal Title: J Toxicol Pathol. 19 Pages: 99-106
• [Journal Article] Prediction of carcinogenic potential by a toxicogenomic approach using rat hepatoma cells. (2006)
  • Author(s): Tsujimura, K.
  • Journal Title: Cancer Sci. 97 Pages: 1002-1010
• [Journal Article] Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) rat hepatocarcinogenesis by caffeine, a CYP1A2 inducer, points to complex counteracting influences. (2006)
  • Author(s): Kuribayashi, M.
  • Journal Title: Cancer Lett., 232・2 Pages: 289-299
• [Journal Article] Differences Between Latent and Clinical Prostate Carcinomas : Lower Cell Proliferation Activity in Latent Cases. (2006)
  • Author(s): Takahashi, S.
  • Journal Title: The Prostate 66 Pages: 211-217
• [Journal Article] Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells (2005)
  • Author(s): Ito, A
  • Journal Title: Cancer Lett 219 Pages: 105-112
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Downregulation of apoptosis revealed by laser microdissection and cDNA microarray analysis of related genesin rat liver preneoplastic lesions (2005)
  • Author(s): Ogawa, K
  • Journal Title: Med.Mol.Morphol 38 Pages: 23-39
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Harman and norhannan suppressed but NaNO2 enhanced the development of preneoplastic livercell foci in 2-amino-3,8-dimethylimidazo[4,5-f] Jquinoxaline (MelQx) treated rats (2005)
  • Author(s): Sugiura, S
  • Journal Title: J.Toxicol.Pathol 18 Pages: 99-104
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Equivocal impact of transplacental and lactational exposure to a food-derived carcinogen,2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine,on prostate and colonlesion development in F344 rats (2005)
  • Author(s): Ikeda, Y
  • Journal Title: Cancer Lett 224 Pages: 23-30
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Influence of atrazineadministration and reduction of calorieintake on prostate carcinogenesis in probasin/SV40 T antigen transgenic rats (2005)
  • Author(s): Kandori, H
  • Journal Title: Cancer Sci 96 Pages: 221-226
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Lack of effects of 1439 MHz electromagnetic near field exposure on the blood-brain barrier in immature and young rats (2005)
  • Author(s): Kurinbayashi, M
  • Journal Title: Bioelectromagnetics 26 Pages: 578-588
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells (2005)
  • Author(s): Ito, A., Asamoto, M., Hokaiwado, N., Takahashi, S., Shirai, T
  • Journal Title: Cancer Lett 219 Pages: 105-112
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Downregulation of apoptosis revealed by laser microdissection and cDNA microarray analysis of related genes in rat liver preneoplastic lesions (2005)
  • Author(s): Ogawa, K., Asamoto, M., Suzuki, S., Tsujimura, K., Shirai, T
  • Journal Title: Med. Mol. Morphol 38 Pages: 23-29
  • NAID: 10018374411
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Harman and norharman suppressed but NaNO2 enhanced the development of preneoplastic liver cell foci in 2-amino-3, 8-dimethylimidazo[4,5-f] quinoxaline (MeIQx)-reated rats (2005)
  • Author(s): Sugiura, S., Asamoto, M., Hokaiwado, N., Hirose, M., Shirai, T
  • Journal Title: J., Toxicol. Pathol 18 Pages: 99-104
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Equivocal impact of transplacental and lactational exposure to a food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-3]pyridine, on prostate and colon lesion development in F344 rats (2005)
  • Author(s): Ikeda, Y., Cho, Y. M., Takahashi, S., Tang, M., Asamoto, M., Ogawa, K., Shirai, T
  • Journal Title: Cancer Lett 224 Pages: 23-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Influence of atrazine administration and reduction of calorie intake on prostate carcinogenesis in probasin/SV4OT antigen transgenic rats (2005)
  • Author(s): Kandori, H., Suzuki, S., Asamoto, M., Murasaki, T., Tang, M., Ogawa, K., Shirai, T
  • Journal Title: Cancer Sci 96 Pages: 221-226
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lack of effects of 1439 MHz electromagnetic near field exposure on the blood-brain barrier in immature and young rats (2005)
  • Author(s): Kuribayashi, M., Wang, J., Fujiwara, O., Doi, Y., Nabae, K., Tamano, S., Ogiso, T., Asamoto, M., Shirai, T
  • Journal Title: Bioelectromagnetics 26 Pages: 578-588
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transgenic disruption of gap junctional intercellular communication protects against hepatotoxicity while increasing susceptibility to liver carcinogenesis in rats, in Carcinogenesis and Modification of Carcinogenesis (2005)
  • Author(s): Asamoto, M., Hokaiwado, N., Shirai, T
  • Journal Title: Edited by T. Tanaka, H. Tsuda. Kerala, Research Signpost Pages: 1-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. (2005)
  • Author(s): Ito, A.
  • Journal Title: Cancer Lett. 219 Pages: 105-112
• [Journal Article] Downregulation of apoptosis revealed by laser microdissection and cDNA microarray analysis of related genes in rat liver preneoplastic lesions. (2005)
  • Author(s): Ogawa, K.
  • Journal Title: Med.Mol.Morphol. 38 Pages: 23-29
• [Journal Article] Harman and norharman suppressed but NaNO2 enhanced the development of preneoplastic liver cell foci in 2-amino-3,8-dimethylimidazo[4,5-fJquinoxaline (MeIQx)-treated rats. (2005)
  • Author(s): Sugiura, S.
  • Journal Title: J.Toxicol.Pathol. 18 Pages: 99-104
• [Journal Article] Equivocal impact of transplacental and lactational exposure to a food-derived carcinogen, 2-amino-l-methyl-6-phenylimidazo[4,5-b]pvridine, on prostate and colon lesion development in F344 rats. (2005)
  • Author(s): Ikeda, Y.
  • Journal Title: Cancer Lett. 224 Pages: 23-30
• [Journal Article] Influence of atrazine administration and reduction of calorie intake on prostate carcinogenesis in probasin/SV40 T antigen transgenic rats. (2005)
  • Author(s): Kandori, H.
  • Journal Title: Cancer Sci. 96 Pages: 221-226
• [Journal Article] Lack of effects of 1439 MHz electromagnetic near field exposure on the blood-brain barrier in immature and young rats. (2005)
  • Author(s): Kuribayashi, M.
  • Journal Title: Bioelectromagnetics. 26 Pages: 578-588
• [Journal Article] Transgenic disruption of gap junction enhances early but not late stage hepatocarcinogenesis in the rat. (2005)
  • Author(s): Hokaiwado, N.
  • Journal Title: Toxicol.Pathol. 33・6 Pages: 695-701
• [Journal Article] Chronic exposure to a 1.439 GHz electromagnetic field used for cellular phones does not promote N-ethylnitrosourea induced central nervous system tumors in F344 rats. (2005)
  • Author(s): Shirai, T.
  • Journal Title: Bioelectromagnetics 26 Pages: 59-68
• [Journal Article] Lack of combination hepatocarcinogenicity of harman, norharman and amitrole when given with NaNO_2 in the rat. (2005)
  • Author(s): Ichihara, T.
  • Journal Title: J.Toxicol.Sci. 30 Pages: 1-6
• [Presentation] Probasin/SV40Tag導入トランスジェニックラット(TRAP)前立腺癌由来ヌードマウス可移植性細胞株の樹立とその性質 (2007)
  • Author(s): 朝元 誠人
  • Organizer: 第18回前立腺がんワークショップ
  • Place of Presentation: 国立がんセンター研究所
  • Year and Date: 2007-09-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Establishment and characterization of rat prostate carcinoma cell lines derived from the Probasin/SV40Tag transgenic rat model (2007)
  • Author(s): Asamoto, M., Hokaiwado, N., Shirai, T
  • Organizer: Proceedings of the 18th Workshop on Prostate Cancer
  • Place of Presentation: Tokyo
  • Year and Date: 2007-09-28
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Carcinogenesis and Modification of Carcinogenesis (2005)
  • Author(s): Asamoto, M
  • Publisher: Kerala:Research Signpost
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Carcinogenesis and Modification of Carcinogenesis (2005)
  • Author(s): Asamoto, M.
  • Publisher: Kerala : Research Signpost