2000 年度実績報告書

日米における乳癌、子宮内膜癌のホルモン環境の検討

研究課題

研究課題/領域番号	12218201
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	原田信広藤田保健衛生大学, 医学部, 教授 (00189705) 鈴木貴東北大学, 大学院・医学系研究科, 助手 (10261629)
キーワード	子宮内膜癌 / エストロゲン / 17水酸化ステロイド脱水素酵素 / レチノイド / ホルモン環境
研究概要	日本人46例、米国ジョンスホプキンス大学医学部のMark Sher man博士から提供された米国人30例の類内膜内膜腺癌において17β-HSD1,2型を免疫組織化学的に検討した。日本人症例では更にthin layer chromatography(TLC)を用いて活性を、RT-PCRを用いて酵素のmRNA発現を検討した。日本人46例では17例(37%)、米国人30例では12例(40%)で癌細胞において17β-HSD2型の発現が認められ、17β-HSD1型は日本人米国人双方でその発現は認められなかった。日本人症例で行ったRT-PCR,TLCを用いた行った活性の検討も免疫組織化学の結果と良く一致した。次に我々はこの17β-HSD2型の発現を制御している最も重要な因子の一つと考えられているレチノイドの受容体であるretinoic acid receptor(RAR)α,β and γ及びretinoid X receptor(RXR)α,β and γの発現をこれらの類内膜型子宮内膜癌で検討して17β-HSD2型の発現動態と相関させた。日米双方の症例ともにこれらのレチノイド受容体の内で癌細胞におけるRXRγの発現がもっとも癌細胞における17β-HSD2型の発現動態と相関している事が判明した。生物学的に活性の高いエストロゲンと低いエストロゲンを相互転換させる17β-HSDのうちエストラジオールをエストロンの方に転換させる2型が日米双方の類内膜型子宮内膜癌では腫瘍局所でのホルモン環境の形成の上で非常に重要な作用を果たしていることが考えられた。叉今回の検討から日米双方の症例ともにRXRγを介したレチノイドの作用が子宮内膜癌の局所での17β-HSD2型の発現の制御に極めて重要な働きをしていることが示唆された。このように類内膜型子宮内膜癌のホルモン環境の日米間の差異の検討において、17β-HSD2型及びその制御機構に関しては共通することが示唆された。

研究成果

(38件)

すべてその他

すべて文献書誌 (38件)

[文献書誌] Takeyama J et al.: "17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus."Joumal 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."Modem 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.: "17 Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma : a correlation to clinicopathological parameters."British Joumal of Cancer. 82. 518-523 (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] Hirasawa G et al.: "11 Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta."Journal of Clinical Endocrinology & Metabolism. 85. 1306-1309 (2000)
[文献書誌] Sone M et al.: "Binding sites for melanin-concentrating hormone in the human brain."Peptides. 21. 245-250 (2000)
[文献書誌] Suzuki S et al.: "Expression of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor in primary lung carcinomas."Anticancer Research. 20. 323-328 (2000)
[文献書誌] Kaaijk EM et al.: "Distribution of steroidogenic enzymes involved in androgen synthesis in polycysticovaries : 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] Arai K et al.: "Adrenal rest tumor of the liver : A case report with immunohistochemical investigation of steroidogenesis."Pathology International. 50. 244-248 (2000)
[文献書誌] Yoshimoto T et al.: "Adrenocortical carcinoma manifesting pure primary aldosteronism : a case report and analysis of steroidogenic enzymes."Journal of Endocrinological Investigation. 23. 112-117 (2000)
[文献書誌] Ariga N et al.: "17 beta-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinoma in 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] Tsubochi H et al.: "Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract."Anticancer Research. 20. 1205-1212 (2000)
[文献書誌] Arihara Z et al.: "Orexin-A in the human brain and tumor tissues of ganglioneuroblastoma and neuroblastoma."Peptides. 21. 565-570 (2000)
[文献書誌] Murakami M et al.: "Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist."Brain Research. 868. 123-127 (2000)
[文献書誌] Matsuzaki S et al.: "Characterization of messenger RNA expression of estrogen receptor-alpha and-beta in patients with ovarian endometriosis."Fertility and Sterility. 73. 1219-1225 (2000)
[文献書誌] Matsuzaki S et al.: "Endomyometriosis arising in the uterosacral ligament : A case report including a literature review and immunohistochemical analysis."Pathology International. 50. 493-496 (2000)
[文献書誌] Semba S et al.: "An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion."Pathology International. 50. 549-552 (2000)
[文献書誌] Sasano H et al.: "Recent advances in surgical pathology of adrenalincidentaloma."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] Iino K et al.: "A case of adrenocortical carcinoma associated with recurrence after laparoscopic surgery."Clinical Endocrinol. 53. 243-248 (2000)
[文献書誌] Yamanaka K et al.: "A case of renin-producing adrenocortical cancer."Endocrine Journal. 47. 119-125 (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 and cellular 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 fortreating 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. 1065-1072 (2000)
[文献書誌] Suzuki T et al.: "3beta-hydroxysteroid dehydrogenase/delta5->4-isomerase activity associated with the human 17 beta-hydroxysteroid dehydrogenase type 2 isoform."Journal of Clinical Endocrinology & Metabolism. 85. 3669-3672 (2000)
[文献書誌] Ohashi Y et al.: "Significance of tumor associated tissue eosinophilia and other inflammatory cell infiltrate in early esophageal squamous cell carcinoma."Anticancer Research. 20. 3025-3030 (2000)
[文献書誌] Takahashi K et al.: "Regional distribution of immunoreactive prolactin-releasing peptide in the human brain."Peptides. 21. 1551-1555 (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)
[文献書誌] Muramatsu Y et al.: "Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa."Peptides. 21. 1799-1809 (2000)
[文献書誌] Suzuki T et al.: "Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex : immunohistochemical studies."Clinical Endocrinology. 53. 739-747 (2000)

2000 年度 実績報告書

日米における乳癌、子宮内膜癌のホルモン環境の検討

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."Joumal 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."Modem 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.: "17 Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma : a correlation to clinicopathological parameters."British Joumal of Cancer. 82. 518-523 (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] Hirasawa G et al.: "11 Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta."Journal of Clinical Endocrinology & Metabolism. 85. 1306-1309 (2000)

[文献書誌] Sone M et al.: "Binding sites for melanin-concentrating hormone in the human brain."Peptides. 21. 245-250 (2000)

[文献書誌] Suzuki S et al.: "Expression of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor in primary lung carcinomas."Anticancer Research. 20. 323-328 (2000)

[文献書誌] Kaaijk EM et al.: "Distribution of steroidogenic enzymes involved in androgen synthesis in polycysticovaries : 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] Arai K et al.: "Adrenal rest tumor of the liver : A case report with immunohistochemical investigation of steroidogenesis."Pathology International. 50. 244-248 (2000)

[文献書誌] Yoshimoto T et al.: "Adrenocortical carcinoma manifesting pure primary aldosteronism : a case report and analysis of steroidogenic enzymes."Journal of Endocrinological Investigation. 23. 112-117 (2000)

[文献書誌] Ariga N et al.: "17 beta-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinoma in 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] Tsubochi H et al.: "Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract."Anticancer Research. 20. 1205-1212 (2000)

[文献書誌] Arihara Z et al.: "Orexin-A in the human brain and tumor tissues of ganglioneuroblastoma and neuroblastoma."Peptides. 21. 565-570 (2000)

[文献書誌] Murakami M et al.: "Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist."Brain Research. 868. 123-127 (2000)

[文献書誌] Matsuzaki S et al.: "Characterization of messenger RNA expression of estrogen receptor-alpha and-beta in patients with ovarian endometriosis."Fertility and Sterility. 73. 1219-1225 (2000)

[文献書誌] Matsuzaki S et al.: "Endomyometriosis arising in the uterosacral ligament : A case report including a literature review and immunohistochemical analysis."Pathology International. 50. 493-496 (2000)

[文献書誌] Semba S et al.: "An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion."Pathology International. 50. 549-552 (2000)

[文献書誌] Sasano H et al.: "Recent advances in surgical pathology of adrenalincidentaloma."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] Iino K et al.: "A case of adrenocortical carcinoma associated with recurrence after laparoscopic surgery."Clinical Endocrinol. 53. 243-248 (2000)

[文献書誌] Yamanaka K et al.: "A case of renin-producing adrenocortical cancer."Endocrine Journal. 47. 119-125 (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 and cellular 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 fortreating 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. 1065-1072 (2000)

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

[文献書誌] Ohashi Y et al.: "Significance of tumor associated tissue eosinophilia and other inflammatory cell infiltrate in early esophageal squamous cell carcinoma."Anticancer Research. 20. 3025-3030 (2000)

[文献書誌] Takahashi K et al.: "Regional distribution of immunoreactive prolactin-releasing peptide in the human brain."Peptides. 21. 1551-1555 (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)

[文献書誌] Muramatsu Y et al.: "Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa."Peptides. 21. 1799-1809 (2000)

[文献書誌] Suzuki T et al.: "Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex : immunohistochemical studies."Clinical Endocrinology. 53. 739-747 (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)