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The elucidation of MPA-induoed inhibition of colorectal cancer growth by hormone replace replacement therapy

Research Project

Project/Area Number 18591836
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

MIBU Ryuichi  Kyushu University, Faculty of Medicine, Professor (20200107)

Co-Investigator(Kenkyū-buntansha) KATO Kiyoko  Kyushu University, Medical Institute of Bioregulation, Lecturer (10253527)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsMPA / Hormone Replacement Therapy / Colorectal Cancer / 更年期医学 / 消化器学
Research Abstract

Numerous epidemiological and experimental studies have suggested the possible effect of female sex hormones against colon cancer risk. The Women's Health Initiative recently reported data from a randomized controlled trial that compared estrogen plus progestin with placebo in postmenpausal women. In this report, therapy with a combination of conjugated equine estrogen(CEE) plus MPA was associated with a significant decrease in the incidence of colorectal cancer, while therapy with CEE alone neither increased nor decreased the incidence of colorectal cancer. However, the precise mechanism by which MPA prevents colorectal cancer remains to be fully investigated. To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro, HT29 and HCT116 human colon cancer cell lines were used in this study. Cell growth and WST-1 assays were performed to investigate the antiproliferative effect of medroxyprogesterone acetate. Cell cycle analysis was performed to investigate the effects of medroxyprogesterone acetate on cell cycle distribution. Western blot, immunoprecipitation and cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins.
Medroxyprogesterone acetate inhibited proliferation of the cancer cells by inducing accumulation in the G0/G1 fraction. Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21, and enhanced interaction of p21 with cyclin-dependent kinase2, eventually inhibiting its activity. Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. These results should help to elucidate the protective effect of medroxyprogesterone acetate on colon cancer risk.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (58 results)

All 2008 2007 2006 2000

All Journal Article (39 results) (of which Peer Reviewed: 17 results) Presentation (13 results) Book (6 results)

  • [Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression2008

    • Author(s)
      Tanaka, et. al.
    • Journal Title

      Menopause (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population2008

    • Author(s)
      Tao, et. al.
    • Journal Title

      Cancer Science 99

      Pages: 355-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 肛門部Paget病患者における肛門管重層扁平上皮部切除術後の直腸肛門機能の検討2008

    • Author(s)
      石川 幹真, ら
    • Journal Title

      日消外会誌 41

      Pages: 277-282

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cyclerelated protein expression2008

    • Author(s)
      Tanaka, et. al.
    • Journal Title

      Menopause (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression2008

    • Author(s)
      Tanaka, et. al.
    • Journal Title

      Menopause 15(in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meat,fish and fat intake in relation to subsite-specific risk of colorectal cancer:The Fukuoka Colorectal Cancer Study2007

    • Author(s)
      Kimura, et. al.
    • Journal Title

      Cancer Science 98

      Pages: 590-597

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phase I/II study of irinotecan and UFT for advanced or metastatic colorectal cancer2007

    • Author(s)
      Mibu, et. al.
    • Journal Title

      Anticancer Research 27

      Pages: 2673-2678

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] HOP/NECC1,a novel regulator of mouse trophoblast differentiation2007

    • Author(s)
      Asanoma, et. al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 24065-24074

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Specific apoptosis induction in HPV-positive cervical carcinoma cells by photodynamic antisense regulation2007

    • Author(s)
      Yamayoshi, et. al.
    • Journal Title

      Oligonucleotides 17

      Pages: 66-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] An inhibitory effect on cell proliferation by blockage ofthe MAPK/Estrogen Receptor/MDM2 signal pathway in gynecologic cancer2007

    • Author(s)
      Suga, et. al.
    • Journal Title

      Gynecologic Oncology 105

      Pages: 341-350

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Characterization of side population cells in human normal endometrium2007

    • Author(s)
      Kato, et. al.
    • Journal Title

      Human Reproduction 22

      Pages: 1214-1223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] ビスフォスフォネート(アレンドロネート)の癌細胞への効果の検討2007

    • Author(s)
      加藤 聖子, ら
    • Journal Title

      Osteoporosis Japan 18

      Pages: 88-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] ここまできた分子標的治療[分子標的治療の臨床応用2]子宮体癌2007

    • Author(s)
      加藤 聖子
    • Journal Title

      臨床婦人科産科 61

      Pages: 1257-1261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] Meat, fish and fat intake in relation to subsite-specific risk of colorectalcancer : The Fukuoka Colorectal Cancer Study2007

    • Author(s)
      Kimura, et. al.
    • Journal Title

      Cancer Science 98

      Pages: 590-597

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] HOP/NECC1, a novel regulator of mouse trophoblast differentiation2007

    • Author(s)
      Asanoma, et. al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 24065-24074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] An inhibitory effect on cell proliferation by blockage of the MAPK/Estrogen Receptor/MDM2 signal pathway in gynecologic cancer2007

    • Author(s)
      Suga, et. al.
    • Journal Title

      Gynecologic Oncology 105

      Pages: 341-350

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phase I/II study of irinotecan and UFT for advanced or metastatic color ectal cancer2007

    • Author(s)
      Mibu, et. al.
    • Journal Title

      Anticancer Research 27

      Pages: 2673-2678

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific apoptosis induction in HPV-positive cervical carcinoma cells By photodynamic antisense regulation2007

    • Author(s)
      Yamayoshi, et. al.
    • Journal Title

      Oligonucleotides 17

      Pages: 66-79

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An inhibitory effect on cell proliferation by blockage of MAPK/Estrogen Receptor/MDM2 signal pathway in gynecologic cancer2007

    • Author(s)
      Suga, et. al.
    • Journal Title

      Gynecologic Oncology 105

      Pages: 341-350

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer : The Fukuoka Colorectal Cancer Study2007

    • Author(s)
      Kimura Y et al.
    • Journal Title

      Cancer Science 98

      Pages: 590-597

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Autofluorescence imaging colonoscopy for the diagnosis of dysplasia in ulcerative colitis2007

    • Author(s)
      Matsumoto T et al.
    • Journal Title

      Inflammatory Bowel Diseases 13

      Pages: 640-641

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Characterization of side population cells (SP cells) in human normal endometrial cells2007

    • Author(s)
      Kato K et al.
    • Journal Title

      Human Reproduction in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] An inhibitory effect on cell proliferation by blockage of the MAPK/Estrogen Receptor/MDM2 signal pathway in gynecologic cancer2007

    • Author(s)
      Suga S et al.
    • Journal Title

      Gynecologic Oncology 105

      Pages: 341-350

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Specific apoptosis induction in HPV-positive cervical carcinoma cells by photodynamic antisense regulation2007

    • Author(s)
      Yamayoshi A et al.
    • Journal Title

      Oligonucleotides in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Physical activity and colorectal cancer:The Fukuoka Colorectal Cancer study2006

    • Author(s)
      Isomura, et. al.
    • Journal Title

      Cancer Science 97

      Pages: 1099-1104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer:bifunctional therapeutic cancer cells2006

    • Author(s)
      Ogura, et. al.
    • Journal Title

      Clinical Cancer Research 12

      Pages: 5216-5223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Loss of the maternal imprint in Dnmt3L(mat-/-) mice leads to a differentiation defect in the extraembryonic tissue2006

    • Author(s)
      Arima, et. al.
    • Journal Title

      Developmental Biology 297

      Pages: 361-373

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The human HVMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice2006

    • Author(s)
      Arima, et. al.
    • Journal Title

      Genomics 88

      Pages: 650-658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 便失禁の診断における排便造影法の工夫2006

    • Author(s)
      壬生 隆一, ら
    • Journal Title

      消化器科 42

      Pages: 436-439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Physical activity and colorectal cancer : The Fukuoka Colorectal Cancer study2006

    • Author(s)
      Isomura, et. al.
    • Journal Title

      Cancer Science 97

      Pages: 1099-1104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer : bifunctional therapeutic cancer cells2006

    • Author(s)
      Ogura, et. al.
    • Journal Title

      Clinical Cancer Research 12

      Pages: 5216-5223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Loss of the maternal imprint in Dnmt3L (mat-/-) mice leads to a differentiation defect in the extraembryonic tissue2006

    • Author(s)
      Arima, et. al.
    • Journal Title

      Developmental Biology 297

      Pages: 361-373

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The human HYMAI/PLAGL1 differentially methylated region acts as animprint control region in mice2006

    • Author(s)
      Arima, et. al.
    • Journal Title

      Genomics 88

      Pages: 650-658

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Physical activity and colorectal cancer : the Fukuoka Colorectal Cancer Study2006

    • Author(s)
      Isomura K et al.
    • Journal Title

      Cancer Science 97

      Pages: 1099-1104

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Loss of the maternal imprint in Dnmt3L(mat-/-) mice leads to differentiation defect in the extraembryonic tissue2006

    • Author(s)
      Arima T et al.
    • Journal Title

      Developmental Biology 297

      Pages: 361-373

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer : bifunctional therapeutic effects on peritoneal cell layer and cancer cells2006

    • Author(s)
      Ogura T et al.
    • Journal Title

      Clinical Cancer Research 12

      Pages: 5216-5223

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Induction on human endometrial cancer cell senescence through modulation of HIF-1 alpha activity by EGLN12006

    • Author(s)
      Kato H et al.
    • Journal Title

      International Journal of Cancer 118

      Pages: 1144-1153

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Activation of STAT3/5 signal pathways in complete mole and repression in choriocarcinoma cell lines2006

    • Author(s)
      Kato H et al.
    • Journal Title

      Journal of Reproductive Medicine 51

      Pages: 41-48

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The Human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice2000

    • Author(s)
      Arima T et al.
    • Journal Title

      Genomics 88

      Pages: 650-658

    • Related Report
      2006 Annual Research Report
  • [Presentation] 直腸肛門痛の病態と近赤外線治療について2007

    • Author(s)
      壬生 隆一
    • Organizer
      第62回日本大腸肛門病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 直腸肛門痛の病態と近赤外線治療について2007

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第62回日本大腸肛門病学会総会 ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2007-11-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] 下部消化管機能障害の多様性について2006

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第31回日本大腸肛門病学会九州地方会
    • Place of Presentation
      熊本
    • Year and Date
      2006-11-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 直腸癌を合併した放射性腸炎の一例2006

    • Author(s)
      工藤暫司, ら
    • Organizer
      日本消化器病学会九州支部例会
    • Place of Presentation
      鹿児島
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ダブルバルーン小腸内視鏡検査で診断したメッケル憩室の一例2006

    • Author(s)
      小川 紘太郎
    • Organizer
      日本消化器病学会九州支部例会
    • Place of Presentation
      鹿児島
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression2006

    • Author(s)
      Tanaka, et. al.
    • Organizer
      The 16th North American Menopause Society (NAMS) Annual Meeting
    • Place of Presentation
      ナッシュビル(米国)
    • Year and Date
      2006-10-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression2006

    • Author(s)
      Tanaka, et. al.
    • Organizer
      The 16th North American Menopause Society(NAMS) Annual Meeting
    • Place of Presentation
      Nashville, USA
    • Year and Date
      2006-10-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 難治性下部消化管機能障害の病態と治療2006

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第48回日本消化器病学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2006-10-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 直腸肛門部痩孔の診断について2006

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第61回日本大腸肛門病学会総会
    • Place of Presentation
      弘前
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 下部消化管機能障害は分類可能か?2006

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第12回大腸肛門機能障害研究会
    • Place of Presentation
      東京
    • Year and Date
      2006-09-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 大腸全摘術後に十二指腸病変を発症した潰瘍性大腸炎の一例2006

    • Author(s)
      藤澤 律子, ら
    • Organizer
      第87回日本消化器病学会九州支部例会
    • Place of Presentation
      佐賀
    • Year and Date
      2006-06-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 肛門からの腫瘤の脱出を主訴とした肛門管扁平上皮癌の2例2006

    • Author(s)
      江口 大樹, ら
    • Organizer
      第43回九州外科学会
    • Place of Presentation
      福岡
    • Year and Date
      2006-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 進行・再発大腸癌に対するCPT-11+UFT併用療法2006

    • Author(s)
      壬生 隆一, ら
    • Organizer
      第106回日本外科学会定期学術集会
    • Place of Presentation
      東京
    • Year and Date
      2006-03-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 今日の治療指針20082008

    • Author(s)
      壬生 隆一
    • Total Pages
      1
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 今日の治療指針20072007

    • Author(s)
      壬生 隆一
    • Total Pages
      1
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 今日の治療のために:ガイドライン外来診療20072007

    • Author(s)
      壬生 隆一
    • Total Pages
      3
    • Publisher
      日経メディカル開発
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] よくわかる卵巣癌のすべて2007

    • Author(s)
      大神 達寛, ら
    • Total Pages
      6
    • Publisher
      永井書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] よくわかる卵巣癌のすべて2007

    • Author(s)
      大神達寛, 加藤聖子, 和氣徳夫
    • Publisher
      永井書店
    • Related Report
      2006 Annual Research Report
  • [Book] 今日の治療指針20062006

    • Author(s)
      壬生 隆一
    • Total Pages
      2
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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