2000 年度実績報告書

ヒト乳癌、子宮内膜癌における腫瘍組織局所でのエストロゲン合成調節機構の解明

研究課題

研究課題/領域番号	11470047
研究機関	東北大学
研究代表者	笹野公伸東北大学, 大学院・医学系研究科, 教授 (50187142)
研究分担者	高橋和広東北大学, 大学院・医学系研究科, 助教授 (80241628) 森谷卓也東北大学, 医学部・附属病院, 助教授 (00230160) 鈴木貴東北大学, 大学院・医学系研究科, 助手 (10261629) 原田信広藤田保健衛生大学, 医学部, 教授 (00189705) 佐藤信二東北大学, 大学院・医学系研究科, 講師 (10142960)
キーワード	子宮内膜癌 / 乳癌 / エストロゲン / 17水酸化ステロイド脱水素酵素 / 子宮内膜増殖症 / レチノイド受容体 / エストロゲン受容体 / プロゲステロン受容体
研究概要	我々は生物学的活性の高いestradiolと低いestoroneとの相互転換に関与する17β-HSD1型、2型の発現、活性をレチノイド、プロゲステロンが制御している事を昨年までの培養細胞を用いたin vitroの研究で明らかにした。そこで本年レチノイドの受容体であるRXRα、β、γ,RARα、β、γ,プロゲステロンの受容体であるPRA,PRBの発現動態を子宮内膜及び乳腺の病変に関して検討した。ヒト乳癌ではレチノイド受容体の内でもRARα,RXRα,RXRβが癌細胞を中心に広範に分布しており、17β-HSD1型、エストロゲン受容体の発現動態との間に有意の相関が認められた。一方子宮内膜癌においてはRARγ、RXRβを除いてすべての受容体が認められたが、腫瘍内エストロゲン代謝に関係する因子との間ではRXRγと17β-HSD2型の間にのみ有意の相関が認められた。一方乳癌におけるPRのsubtypesはPRA,PRB共にほぼ同等の比率で癌細胞で発現していた。エストロゲン受容体との間に相関関係は認められたが、17β-HSD1型との間に有意な相関は認めれなかった。一方子宮内膜癌の方ではPRAよりもPRBの発現の方が高く、PRBの発現動態と17β-HSD2型の発現との間には有意の相関が認められた。このようにレチノイド及びプロゲステロンは実際のヒト子宮内膜癌、乳癌における腫瘍内のエストロゲン産生代謝動態においても重要な役割を果たしている事が考えられた。

研究成果
(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] Takeyama J et al.: "17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus."Journal of Clinical Endocrinology & Metabolism. 85. 410-416 (2000)
[文献書誌] Moriya T et al.: "Immunohistochemical analysis of Ki-67,p53,p21,and p27 in benign and malignantapocrine lesions of the breast : its correlation to histologic findings in 43 cases."Modern Pathology. 13. 13-18 (2000)
[文献書誌] Kimura K et al.: "Ultrastructure of cells undergoing apoptosis."Vitamin and Hormore. 58. 257-266 (2000)
[文献書誌] Suzuki T et al.: "17Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma : a correlation to clinicopathological parameters."British Joumal of Cancer. 82. 518-52 (2000)
[文献書誌] Speiser PW et al.: "Ovarian hyperthecosis in the setting of portal hypertension."Journal of Clinical Endocrinology & Metabolism. 85. 873-877 (2000)
[文献書誌] Kaaijk EM et al.: "Distribution of steroidogenic enzymes involved in androgen synthesis in polycystic ovaries : an immunohistochemical study."Molecular Human Reproduction. 6. 443-447 (2000)
[文献書誌] Tashiro A et al.: "Expression and activity of dehydroepiandrosterone sulfotransferase in human gastric mucosa."Journal of Steroid Biochemistry Molecular Biology. 72. 149-154 (2000)
[文献書誌] Ariga N et al.: "17 beta-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinomain situ and intraductal proliferative lesions of the human breast."Anticancer Research. 20. 1101-1108 (2000)
[文献書誌] Iwabuchi M et al.: "Serrated adenoma : a clinicopathological, DNA ploidy, and immunohistochemical study."Anticancer Research. 20. 1141-1147 (2000)
[文献書誌] Sasano H et al.: "Recent advances in surgical pathology of adrenal incidentaloma."Biomed & Pharmacother. 54. 169s-174s (2000)
[文献書誌] Bulun SE et al.: "Estrogen biosynthesis in endometriosis : molecular basis and clinical relevance."Journal of Molecular Endocrinology. 25. 35-42 (2000)
[文献書誌] Suzuki T et al.: "Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders."Journal of Clinical Endocrinology & Metabolism. 85. 2752-2757 (2000)
[文献書誌] Hasegawa T et al.: "Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice."Molecular Endocrinology. 14. 1462-1471 (2000)
[文献書誌] Suzuki T et al.: "Immunohistochemical distribution of chicken ovalbumin upstream promoter transcription factor II in human tissues."Molecular and cellular Endocrinology. 164. 69-75 (2000)
[文献書誌] Bulun SE et al.: "Molecular basis for treating endometriosis with aromatase inhibitors."Human Reproduction Update. 6. 413-418 (2000)
[文献書誌] Kato M et al.: "Mechanism of anti-tumor effect of combination of bleomycin and shock waves."Japanese Journal of Cancer Research. 91. 1065-7102 (2000)
[文献書誌] Suzuki T et al.: "3beta-hydroxysteroid dehydrogenase/delta5->4-isomerase activity associated with the human 17beta-hydroxysteroid dehydrogenase type 2 isoform."Journal of Clinical Endocrinology & Metabolism. 85:. 3669-3672 (2000)
[文献書誌] Akahira J et al.: "Progesterone receptor isoforms A and B in human epithelial ovarian carcinoma : immunohistochemical and RT-PCR studies."British Journal of Cancer. 83. 1488-1494 (2000)
[文献書誌] Ariga N et al.: "Retinoic Acid Receptor and Retinoid X Receptor in Ductal Carcinoma in situ and Intraductal Proliferative Lesions of the Human Breast."Japanese Journal of Cancer Research. 91. 1169-1176 (2000)
[文献書誌] Sasano H et al.: "17-Beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma.a new development in intracrinology."Oncology. 59. 5-12 (2000)
[文献書誌] Utsunomiya H et al.: "Analysis of estrogen receptor alpha and beta in endometrial carcinomas : correlation with ER beta and clinicopathologic findings in 45 cases."International Journal of Gynecological Pathology. 19:. 335-341 (2000)

2000 年度 実績報告書

ヒト乳癌、子宮内膜癌における腫瘍組織局所でのエストロゲン合成調節機構の解明

研究代表者

笹野 公伸 東北大学, 大学院・医学系研究科, 教授 (50187142)

研究成果

[文献書誌] Takeyama J et al.: "17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus."Journal of Clinical Endocrinology & Metabolism. 85. 410-416 (2000)

[文献書誌] Moriya T et al.: "Immunohistochemical analysis of Ki-67,p53,p21,and p27 in benign and malignantapocrine lesions of the breast : its correlation to histologic findings in 43 cases."Modern Pathology. 13. 13-18 (2000)

[文献書誌] Kimura K et al.: "Ultrastructure of cells undergoing apoptosis."Vitamin and Hormore. 58. 257-266 (2000)

[文献書誌] Suzuki T et al.: "17Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma : a correlation to clinicopathological parameters."British Joumal of Cancer. 82. 518-52 (2000)

[文献書誌] Speiser PW et al.: "Ovarian hyperthecosis in the setting of portal hypertension."Journal of Clinical Endocrinology & Metabolism. 85. 873-877 (2000)

[文献書誌] Kaaijk EM et al.: "Distribution of steroidogenic enzymes involved in androgen synthesis in polycystic ovaries : an immunohistochemical study."Molecular Human Reproduction. 6. 443-447 (2000)

[文献書誌] Tashiro A et al.: "Expression and activity of dehydroepiandrosterone sulfotransferase in human gastric mucosa."Journal of Steroid Biochemistry Molecular Biology. 72. 149-154 (2000)

[文献書誌] Ariga N et al.: "17 beta-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinomain situ and intraductal proliferative lesions of the human breast."Anticancer Research. 20. 1101-1108 (2000)

[文献書誌] Iwabuchi M et al.: "Serrated adenoma : a clinicopathological, DNA ploidy, and immunohistochemical study."Anticancer Research. 20. 1141-1147 (2000)

[文献書誌] Sasano H et al.: "Recent advances in surgical pathology of adrenal incidentaloma."Biomed & Pharmacother. 54. 169s-174s (2000)

[文献書誌] Bulun SE et al.: "Estrogen biosynthesis in endometriosis : molecular basis and clinical relevance."Journal of Molecular Endocrinology. 25. 35-42 (2000)

[文献書誌] Suzuki T et al.: "Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders."Journal of Clinical Endocrinology & Metabolism. 85. 2752-2757 (2000)

[文献書誌] Hasegawa T et al.: "Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice."Molecular Endocrinology. 14. 1462-1471 (2000)

[文献書誌] Suzuki T et al.: "Immunohistochemical distribution of chicken ovalbumin upstream promoter transcription factor II in human tissues."Molecular and cellular Endocrinology. 164. 69-75 (2000)

[文献書誌] Bulun SE et al.: "Molecular basis for treating endometriosis with aromatase inhibitors."Human Reproduction Update. 6. 413-418 (2000)

[文献書誌] Kato M et al.: "Mechanism of anti-tumor effect of combination of bleomycin and shock waves."Japanese Journal of Cancer Research. 91. 1065-7102 (2000)

[文献書誌] Suzuki T et al.: "3beta-hydroxysteroid dehydrogenase/delta5->4-isomerase activity associated with the human 17beta-hydroxysteroid dehydrogenase type 2 isoform."Journal of Clinical Endocrinology & Metabolism. 85:. 3669-3672 (2000)

[文献書誌] Akahira J et al.: "Progesterone receptor isoforms A and B in human epithelial ovarian carcinoma : immunohistochemical and RT-PCR studies."British Journal of Cancer. 83. 1488-1494 (2000)

[文献書誌] Ariga N et al.: "Retinoic Acid Receptor and Retinoid X Receptor in Ductal Carcinoma in situ and Intraductal Proliferative Lesions of the Human Breast."Japanese Journal of Cancer Research. 91. 1169-1176 (2000)

[文献書誌] Sasano H et al.: "17-Beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma.a new development in intracrinology."Oncology. 59. 5-12 (2000)

[文献書誌] Utsunomiya H et al.: "Analysis of estrogen receptor alpha and beta in endometrial carcinomas : correlation with ER beta and clinicopathologic findings in 45 cases."International Journal of Gynecological Pathology. 19:. 335-341 (2000)

2000 年度実績報告書

笹野公伸東北大学, 大学院・医学系研究科, 教授 (50187142)