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Establishment of breast cancer prevention protocol based on hormone milieu of pregnancy and elucidation of its molecular mechanisms

Research Project

Project/Area Number 17591361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKansai Medical University

Principal Investigator

TSUBURA Airo  Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (90098137)

Co-Investigator(Kenkyū-buntansha) MATSUOKA Yoichiro  Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60219409)
UEHARA Norihisa  Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (30368211)
TAKASHI Yuri  Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50330212)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsPregnancy / Estrogen / Progesterone / Rat / N-methyl-N-nitrosourea / Mammary / Cancer / Duration / MNU / Lewis rat / Carcinoma / estrogen / progesterone
Research Abstract

Early age at first full-term pregnancy inversely correlates with breast cancer risk. The protective effects of pregnancy against mammary cancer can be mimicked in the rat by short-term treatment (21 days or slightly longer) with estrogen and progesterone. However, there have been no precise evaluations of the effects of different durations of exposure to pregnancy levels of estrogen and progesterone on mammary carcinogenesis risk. Female Lewis rats were administered a single intraperitoneal injection of 50 mg/kg MNU at 28 days of age, and then were either left hormone-untreated (control group), or underwent subcutaneous implantation of a 21-day release pellet containing 0.5 mg 17 β-estradiol and 32.5 mg progesterone (E/P pellet) at 42 days of age. The pellet was either replaced every 3 to 4 weeks throughout the experimental period (long-term E/P group), or was implanted only once (short-term group). The rat were sacrificed when they developed a mammary tumor with a diameter of 【greater than or equal】 1cm, or when they reached the age of 29 weeks. In rats implanted with a single E/P pellet, circulating 17β -estradiol and progesterone reached pregnancy levels 2 weeks after implantation, but returned to control levels 8 weeks after implantation. Rats that received long-or short-term E/P treatment had a decreased incidence of mammary carcinoma with a diameter of 【greater than or equal】 1 cm, compared to control rats. However, when histologically detected microcarcinomas (diameter <1 cm) were included for comparison, the E/P-treated groups exhibited an abrupt increase in the number of microcarcinomas from 22 to 25 weeks after MNU injection. Although short-term E/P treatment significantly suppressed mammary carcinomas of all sizes, long-term E/P treatment had no cancer-suppressing effect. Thus, the duration of E/P treatment is an essential factor for the suppression of mammary carcinogenesis.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (9 results)

All 2007 2006 Other

All Journal Article (9 results)

  • [Journal Article] Multistep mouse mammary tumorigenesis through preneoplasia to neoplasia and acquisition of metastatic potential.2007

    • Author(s)
      Tsubura A, Yoshizawa K, Uehara N, Yuri T, Matsuoka Y
    • Journal Title

      Med Mol Morphol 40(1)

      Pages: 9-17

    • NAID

      10024379323

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats.2006

    • Author(s)
      Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubura A
    • Journal Title

      In Vivo 20 (6B)

      Pages: 829-836

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells.2006

    • Author(s)
      Yuri T, Tsukamoto R, Miki K, Uehara N, Matsuoka Y, Tsubura A.
    • Journal Title

      Oncol Rep 16(6)

      Pages: 1307-1312

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of different durations of estrogen and progesterone treatment on development of Nmethyl-Nnitrosourea-induced mammary carcinomas in female Lewis rats.2006

    • Author(s)
      Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubura A.
    • Journal Title

      In Vivo 20

      Pages: 829-836

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats.2006

    • Author(s)
      Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubara A
    • Journal Title

      In Vivo 20(6B)

      Pages: 829-836

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells.2006

    • Author(s)
      Yuri T, Tsukamoto R, Miki K, Uehara N, Mtsuoka Y, Tsubura A
    • Journal Title

      Oncol Rep 16(6)

      Pages: 1307-1312

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Parous mammary glands exhibit distinct alterations in gene expression and proliferation responsiveness to carcinogenic stimuli in Lewis rats2006

    • Author(s)
      Uehara N, Unami A, Kiyozuka Y, Shikata N, Oishi Y, Tsubura A.
    • Journal Title

      Oncol Rep (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Multistep mouse mammary tumorigenesis through preneoplasia to neoplasia and acquisition of metastatic potential.

    • Author(s)
      Tsubura A, Yoshizawa K, Uehara N, Yuri T, Matsuoka Y
    • Journal Title

      Med Mol Morphol (in press)

    • NAID

      10024379323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multistep mouse mammary tumorigenesis through preneoplasia to neoplasia and acquisition of metastatic potential.

    • Author(s)
      Tsubura A, Yoshizawa K, Uehara N, Yuri T, Matsuoka Y.
    • Journal Title

      Med Mol Morphol (in press)

    • NAID

      10024379323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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