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Experimental Study on Overcoming Resistance to Hormonal Therapy in Breast Cancer

Research Project

Project/Area Number 12671187
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKAWASAKI MEDICAL SCHOOL

Principal Investigator

KUREBAYASHI Jyunichi  Kawasaki Medical School,Surgery,Associate professor, 医学部, 助教授 (10248255)

Co-Investigator(Kenkyū-buntansha) OTSUKI Takemi  Kawasaki Medical School, Hygiene, Associate Professor, 医学部, 助教授 (40160551)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsBreast Cancer / Hormone Resistance / Hypoxia / Estrogen Receptor / Hypoxia-inducible Factor-Iα / Vascular Endothelial Growth Factor / Progesterone Recepter / Cell Line / VEGF / 低酸素環境
Research Abstract

We have advocated the significant role of overexpression of angiogenic factors, such as VEGF and FGF, in the development of resistance to hormonal therapy in breast cancer. Recent studies have suggested that a hypoxic microenvironment plays an important role in the progression of malignant cells. Therefore, we hypothesized that the hypoxic microenvironment, which enhances the expression ofangiogenic factors, may cause the resistance to hormonal therapy in breast cancer. Our recent studies revealed some evidence supporting our hypothesis as follows : 1) hypoxia post-transcriptionally and time-dependently down-regulated the expression of estrogen receptor (ER)- a and its functions, such as growth-stimulation and progesterone receptor-induction by estradiol, 2) hypoxia also decreased the growth-inhibitory effect of antiestrogen and a progestin, medroxyprogesterone acetate, 3) in breast cancer tissues, immunohistochemical analysis revealed that the expression level of a hypoxia marker, hypoxia-inducible factor (HIF)-l a, inversely correlated with the expression level of ER- a in breast cancer cells. In addition, we conducted a study investigating the effects of a novel Hsp90 inhibitor, KF58333 provided from Kyowa Hakko Kogyo Co., Ltd. We have found for the first time that this agent down-regulated a protein expression level of HIF-1 a. and VEGF in a hormone-resistant human breast cancer cell line, KPL-1, which was established in our institute. Findings from our recent studies suggest that hypoxic microenviromnment induces the development of hormone resistance in breast cancer and a certain agent, which inhibits HIF-1 a expression, may overcome such resistance. Further studies using hypoxic toxins are under investigation in our laboratory to clarify our hypothesis and to find promising agents, which can overcome the resistance to hormonal therapy in breast cancer.

Report

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

    (52 results)

All Other

All Publications (52 results)

  • [Publications] Kurebayashi, J: "Hypoxia reduces hormone responsiveness of human breat cancer cells"Japanese Journal of Cancer Research. 92・10. 1093-1101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "A radicicol derivative, KF58333,inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, angiogenesis and growth of human breast cancer xenografts"Japanese Journal of Cancer Research. 92・12. 1342-1351 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "低酸素環境下における乳癌のホルモン感受性低下に関する基礎的研究"乳癌基礎研究. 10. 56-61 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "乳癌ホルモン療法の現状と展望"日本医事新報. 4025. 20-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "内分泌療法抵抗性乳癌に対する治療戦略"Breast Cancer Today. 18・1. 2-8 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "乳癌におけるhypoxia-inducible factor (HIF)-1αの発現"乳癌基礎研究. 11(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] 紅林 淳一: "乳癌のホルモン療法"外科治療. (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] Soga, S: "Stereo-specific antitumor activity of radicicol oxime derivatives"Cancer Chemotherapy & Pharmacology. 48. 435-445 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, S: "Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts"Cancer Chemotherapy & Pharmacology. 48. 283-288 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 園尾 博司: "進行・再発乳癌のホルモン療法"癌と化学療法. 28・7. 909-926 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "Biological and clinical significance of HER2 overexpression in breast cancer"Breast Cancer. 8・1. 45-21 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "Regulation of interleukin-6 secretion from breast cancer cells and its clinical implication"Breast Cancer. 7・2. 124-129 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "Paradoxical hormone-responses of KPL-1 breast cancer cells in vivo : a significant role of angiogenesis in tumor growth"Oncology. 59・2. 158-165 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "Endocrine therapies for patients with recurrent breast cancer : predictive factors for responses to first-and second-line endocrine therapies"Oncology. 59(Suppl 1). 31-37 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "乳癌細胞株におけるER-α、ER-β、転写共役因子の発現とホルモン感受性"乳癌基礎研究. 9. 15-19 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoo, H: "Predictive factors for response to endocrine therapy in patients with recurrent breast cancer"Breast Cancer. 7・4. 297-301 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 紅林 淳一: "非浸潤性乳管癌の基礎と臨床"篠原出版新社. 7/221 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Hypoxia reduces hormone responsiveness of human breast cancer cells."Japanese Journal of Cancer Research. 92(10). 1093-1101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "A radicicol derivative, KF58333, inhibits expression ofhypoxia-inducible factor-1 a. and vascular endothelial growth factor, angiogenesis anfl growth of human breast cancer xenografts."Japanese Journal of Cancer Research. 92(12). 1342-1351 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "An experimental study on hormone-resistance in breast cancer under hypoxic conditions."Basic Investigation of Breast Carcinoma. 10. 56-61 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Present status and future perspectives of hormone therapy for breast cancer."Nihon-Iji-Shinpo. 4025. 20-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Strategies against hormone-refractory breast cancer."Breast Cancer Today. 18(1). 2-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Expression ofhypoxia-inducible factor (HIF)-1α in breast cancer tissues."Basic Investigation of Breast Carcinoma. 11. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Hormone therapy for breast cancer."Geka-Chiryo. 2002. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Soga, S.: "Stereo-specific antitumor activity of radicicol oxime derivatives"Cancer Chemotherapy&Pharmacology. 48. 435-445 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, S.: "Combined effects ofdocetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts."Cancer Chemotherapy&Pharmacology. 48. 283-288 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoo, H.: "Hormone tnerapy for advanced breast cancer."Japanese Journal of Cancer Research. 28(7). 909-926 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Biological and clinical significance of HER2 overexpression in breast cancer."Breast Cancer. 8(1). 45-51 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Regulation of interleukin-6 secretion from breast cancer cells and its clinical implication."Breast Cancer. 7(2). 124-129 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Paradoxical hormone-resp9nses of KPL- 1 breast cancer cells in vivo : a significant role of angiogenesis in tumor growth."Oncology. 59(2). 158-165 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Endocrine therapies for patients with recurrent breast cancer : predictive factors for responses to first- and second-line endocrine therapies."Oncology. 59(Suppl 1). 31-37 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Relationship between hormone-sensitivity and expression levels of ER- α, ER- β and cofactors in breast cancer."Basic Investigation of Breast Carcinoma. 9. 15-19 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoo, H.: "Predictive factors for response to endocrine therapy in patients with recurrent breast cancer."Breast Cancer. 7(4). 297-301 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J.: "Basic Science and Clinical Significance of Ductal Carcinoma in situ"Shinohara- Shuppan-Shinsha,. 221 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurebayashi, J: "Hypoxia reduces hormone responsiveness of human breast cancer cells"Japanese Journal of Cancer Research. 92・10. 1093-1101 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurebayashi, J: "A radicicol derivative, KF58333, inhibits expression of hypoxia-inducible factor-1 α and vascular endothelial growth factor, angiogenesis and growth of human breast cancer xenografts"Japanese Journal of Cancer Research. 92・12. 1342-1351 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "低酸素環境下における乳癌のホルモン感受性低下に関する基礎的研究"乳癌基礎研究. 10. 56-61 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "乳癌ホルモン療法の現状と展望"日本医事新報. 4025. 20-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "内分泌療法抵抗性乳癌に対する治療戦略"Breast Cancer Today. 18・1. 2-8 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "乳癌におけるhypoxia-inducible factor(HIF)-1αの発現"乳癌基礎研究. 11(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "乳癌のホルモン療法"外科治療. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Soga, S: "Stereo-specific antitumor activity of radicicol oxime derivatives"Cancer Chemotherapy & Pharmacology. 48. 435-445 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, S: "Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts"Cancer Chemotherapy & Pharmacology. 48. 283-288 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 園尾 博司: "進行・再発乳癌のホルモン療法"癌と化学療法. 28・7. 909-926 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林 淳一: "非浸潤性乳管癌の基礎と臨床"篠原出版新社. 7/221 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紅林淳一: "低酸素環境下における乳癌のホルモン感受性低下に関する基礎的研究"乳癌基礎研究. 10(in Press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurebayashi,J.: "Biological and clinical significance of HER2 overexpression in breast cancer"Breast Cancer. 8(1). 45-51 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurebayashi,J.: "Regulation of interleukin-6secretion from breast cancer cells and its clinical implication"Breast Cancer. 7(2). 124-129 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurebayashi,J.: "Paradoxical hormone-responses of KPL-1 breast cancer cells in vivo : a significant role of angiogenesis in tumor growth"Oncology. 59(2). 158-165 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurebayashi,J.: "Endocrine therapies for patients with recurrent breast cancer : predictive factors for responses to first-and second-line endocrine therapies"Oncology. 59(Suppl1). 31-37 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 紅林淳一: "乳癌細胞株におけるER-α、ER-β、転写共役因子の発現とホルモン感受性"乳癌基礎研究. 9. 15-19 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 紅林淳一: "非浸潤性乳管癌の生物学的悪性度:血管新生、VEGF発現との関連.非浸潤性乳管癌の基礎と臨床"篠原出版新社(in Press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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