肺がんとエストロゲン-癌局所でのホルモン産生と作用機序の解明-

2007 Fiscal Year Annual Research Report

• Project/Area Number: 18390109
• Research Institution: Tohoku University
• Principal Investigator: 笹野 公伸 Tohoku University, 大学院・医学系研究科, 教授 (50187142)
• Co-Investigator(Kenkyū-buntansha): 鈴木 貴 東北大学, 医学部, 教授 (10261629) ; 林 慎一 東北大学, 医学部, 教授 (60144862) ; 三木 康宏 東北大学, 大学院・医学系研究科, 助教 (50451521)
• Keywords: 肺 / エストロゲン / 腫瘍 / 癌 / 受容体 / ホルモン / 細胞増殖 / アロマターゼ

Research Abstract

1、肺癌組織におけるエストロゲン合成酵素aromataseの局在性の検討
ヒト肺癌6例(いずれも腺癌)について、Laser Capture Microdissecition(LCM)にて癌細胞と間質細胞から各々RNAを抽出し、定量的PCR(LightCycler)にてaromataseの発現量を比較した。全ての症例で癌細胞にaromataseの発現を認めた。間質細胞では3例にaromataseの発現が認められず、癌細胞での発現よりも有意に低かった(p<0.05)。
2、肺癌培養細胞株におけるaromatase依存性増殖の検討
昨年までの検討でaromataseの発現が認められたLK87を本検討では使用した。LK87にtestosterone単独(1pMから1nM:公比10)、testosteron十5mM flutamide(androgen受容体阻害剤)、testosteron+5mM flutamide+10nM letrozole(aromatase阻害剤)をそれぞれ添加し、72時間後に(3)と同様に細胞増殖を評価した。Testosteroneに対する反応性では、10〜1000pM Testosteroneの添加によって溶媒対照と比較して有意な細胞増殖の抑制が確認された。LK87においてはandrogen受容体が発現(定量的PCR)していることを確認しており、この増殖抑制効果はandrogenとしての直接作用と考えられた。また、testosteron十flutamide添加によって、1pM testosteroh添加からLK87の細胞増殖が認められた。さらにこのandrogen受容体阻害状況下でのtestosteroneによる細胞増殖作用は、aromatase阻害剤(letrozole)によって抑制された

Research Products

• [Journal Article] Intratumoral estrogen and estrogen receptors in human non-small cell lung carcinoma (2008)
  • Author(s): H. Niikawa, T. Suzuki, Y. Miki, S. Suzuki, S. Nagasaki, J-I. Akahira, S. Honma, D. B. Evans, S-I. Hayashi, T. Kondo, H. Sasano
  • Journal Title: Clinical Cancer Research (in press)
  • Peer Reviewed
• [Journal Article] Primary aldosteronism due to unilateral adrenal microadenoma in an elderly patient: efficacy of selective adrenal venous sampling. (2008)
  • Author(s): Tamura Y, Adachi J, Chiba Y, Mori S, Takeda K, Kasuya Y, Murayama T, Sawabe M, Sasano H, Araki A, Ito H, Horiuchi T.
  • Journal Title: Intern Med 47 Pages: 37-42
  • Peer Reviewed
• [Journal Article] Multiple unilateral adrenal adenomas in a patient with primary hyperaldosteronism. (2008)
  • Author(s): Leung AM, Sasano H, Nishikw a T, McAneny DB, Malabanan AO.
  • Journal Title: Endocr Pract 14 Pages: 76-79
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• [Journal Article] Endogenous Secretory Receptor for Advanced Glycation Endproducts in Non-Small Cell Lung Carcinoma. (2007)
  • Author(s): Kobayashi S, Kubo H, Suzuki T, Ishizawa K, Yamada M, He M, Yamamoto Y, Yamamoto H, Sasano H, Sasaki H, Suzuki S.
  • Journal Title: American journal of respiratory and critical care medicine. 175 Pages: 184-189
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• [Journal Article] 5alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. International journalof cancer. (2007)
  • Author(s): Suzuki T, Miki Y, Moriya T, Akahira JI, Ishida T, Hirakawa H, Yamaguchi Y, Hayashi SI, Sasano H.
  • Journal Title: Journal international du cancer. 120 Pages: 285-291
  • Peer Reviewed
• [Journal Article] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: A possible androgenic bone protective effects (2007)
  • Author(s): Miki Y, Suzuki T, Hatori M, Igarashi K, Aisaki KI, Kanno J, Nakamura Y, Uzuki M, Sawai T, Sasano H.
  • Journal Title: Bone 40 Pages: 876-887
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• [Journal Article] Bone Marrow(BM)Transplantation Promotes{beta}Cell Regeneration after Acute Injury through BM Cell Mobilization. (2007)
  • Author(s): Hasegawa Y, Ogihara T, Yamada T, Ishigaki Y, Imai J, Uno K, Gao J, Kaneko K, Ishihara H, Sasano H, Nakauchi H, Oka Y, Katagir
  • Journal Title: Endocrinology 148 Pages: 2006-2015
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• [Journal Article] Promoter methylation status of the Cyclin D2 gene is associated with poor prognosis in human epithelial ovarian cancer. (2007)
  • Author(s): Sakuma M, Akahira J, Ito K, Niikura H, Moriya T, Okamura K, Sasano H, Yaegashi N.
  • Journal Title: Cancer science 98 Pages: 380-386
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• [Journal Article] Expression of adrenomedullin2/intermedin in human brain, heart, and kidney. (2007)
  • Author(s): Morimoto R, Satoh F, Murakami O, Totsune K, Suzuki T, Sasano H, Ito S, Takahashi K.
  • Journal Title: Peptides 28 Pages: 1095-1103
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• [Journal Article] Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor. (2007)
  • Author(s): Suzuki T, Urano T, Miki Y, Moriya T, Akahira J, Ishida T, Horie K, Inoue S, Sasano H
  • Journal Title: Cancer Science 98 Pages: 644-651
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• [Journal Article] Vaginal tumors with histologic and immunocytochemical feature of gastrointestinal stromal tumor: two cases and review of the literature. (2007)
  • Author(s): Nagase S, Mikami Y, Moriya T, Niikura H, Yoshinaga K, Takano T, Ito K. Akahira J, Sasano H, Yaegashi N.
  • Journal Title: International Journal of Gynecological Cancer 17 Pages: 928-933
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• [Journal Article] Possibly Simultaneous Primary Aldosteronism and Preclinical Cushing's Syndrome in a Patient with Double Adenomas of Right Adrenal Gland. (2007)
  • Author(s): Saito T, Ikoma A, Saito T, Tamemoto H, Suminaga Y, Yamada S, Kawakami M, Suzuki T, Sasano H, Ishikawa SE.
  • Journal Title: Endocr J 54 Pages: 287-293
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• [Journal Article] Benign cortisol-secreting adrenocortical adenomas produce small amounts of androgens. (2007)
  • Author(s): Kamenicky P, Houdoin L, Ferlicot S, Salenave S, Brailly S, Droupy S, Meduri G, Sasano H, Suzuki T, Young J, Chanson P.
  • Journal Title: Clinical Endocrinology 66 Pages: 778-788
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• [Journal Article] Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cel (2007)
  • Author(s): Miki Y, Suzuki T, Tazawa C, Yamaguchi Y, Kitada K, Honma S, Moriya T, Hirakawa H, Evans DB, Hayashi S, Ohuchi N, Sasano H.
  • Journal Title: Cancer Research 67 Pages: 3945-3954
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• [Journal Article] Reliability of prognostic factors in breast carcinoma determined by core needle biopsy. (2007)
  • Author(s): Usami S, Moriya T, Amari M, Suzuki A, Ishida T, Sasano H, Ohuchi N.
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• [Journal Article] Ovarian epithelial carcinoma with estrogen-producing stroma. (2007)
  • Author(s): Tokunaga H, Akahira J, Suzuki T, Moriya T, Sasano H, Ito K, Yaegashi N.
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• [Journal Article] Preclinical Cushing's Syndrome Resulting from Adrenal Black Adenoma Diagnosed with Diabetic Ketoacidosis. (2007)
  • Author(s): Kahara T, Seto C, Uchiyama A, Usuda D, Akahori H, Tajika E, Miwa A, Usuda R, Suzuki T, Sasano H.
  • Journal Title: Endocr J 54 Pages: 543-551
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• [Journal Article] Controversies of aromatase localization in human breast cancer-Stromal versus parenchymal cells. (2007)
  • Author(s): Miki Y, Suzuki T, Sasano H.
  • Journal Title: The Journal of Steroid Biochemistry and Molecular Biology 106 Pages: 97-101
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• [Journal Article] Medicolegal Liability in pathology: an international perspective. (2007)
  • Author(s): Wick MR, Foucar E, Allen PW, Alves VA, . Bjornsson J, Bosman F, Churg AW, Drut R, Foster CS, Hauptmann S, Hytiroglou P, Kuo TT, Matsubara O, Nappi O, Pervez S, Rosai J, Sasano H, Vielh P, Zelger B.
  • Journal Title: Seminars in Diagnostic Pathology 24 Pages: 65-76
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• [Journal Article] Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor. (2007)
  • Author(s): Suzuki T, Inoue A, Miki Y, Moriya T, Akahira J, Ishida T, Hirakawa H, Yamaguchi Y, Hayashi S, Sasano H.
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• [Journal Article] Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma. (2007)
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• [Journal Article] Somatostatin receptor subtypes in human non-functioning neuroendocrine tumors and effects of somatostatin analogue SOM230 on cell proliferation in cell line NCI-H727. (2007)
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• [Journal Article] Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma. (2007)
  • Author(s): Muto M, Onogawa T, Suzuki T, Ishida T, Rikiyama T, Katayose Y, Ohuchi N, Sasano H, Abe T, Unno M.
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• [Journal Article] Transcription Factor GATA-6 in the Human Adrenocortex: Association with Adrenal Development and Aging. (2007)
  • Author(s): Nakamura Y, Suzuki T, Sasano H.
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• [Journal Article] Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma-New Developments in Potential Endocrine Therapy for Endometrial Cancer- (2007)
  • Author(s): Ito K, Utsunomiya H, Yaegashi N, Sasano H.
  • Journal Title: Endocr J 54 Pages: 667-679
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• [Journal Article] In situ production of sex steroids in human breast carcinoma. (2007)
  • Author(s): Suzuki T, Miki Y, Moriya T, Akahira J, Hirakawa H, Ohuchi N, Sasano H.
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• [Journal Article] Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. (2007)
  • Author(s): LooWT. Sasano H. ChowLW
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• [Journal Article] Aromatase inhibitor and bone. (2007)
  • Author(s): Miki Y, Suzuki T, Sasano H.
  • Journal Title: Biomedicine & Pharmacotherapy 61 Pages: 540-542
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• [Journal Article] Analysis of surrogate markers for target-specific therapy in breast carcinomas using archival materials. (2007)
  • Author(s): Sasano H, Suzuki T, Moriya T.
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• [Journal Article] Evaluation of therapeutic efficacy of capecitabine on human breast carcinoma tissues and cell lines in vitro. (2007)
  • Author(s): LooWT. Sasano H. ChowLW,
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• [Journal Article] Decreased expression of RIZI and its clinicopathological significance inepithelial ovarian carcinoma: Correlation with epigenetic inactivation by aberrant DNA methylation. (2007)
  • Author(s): Akahira J, Suzuki F, Suzuki T, Miura I, Kamogawa N, Miki Y, Ito K, Yaegashi N, Sasano H.
  • Journal Title: Pathology International 57 Pages: 725-733
  • Peer Reviewed
• [Journal Article] Intracrinology of estrogens and androgens in breast carcinoma. (2007)
  • Author(s): Sasano H, Suzuki T, Miki Y, Moriya T.
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• [Journal Article] Hormonal markers in breast cancer: coexpression, relationship with pathologic characteristics, and risk factor associations in a population-basedstudy. (2007)
  • Author(s): Yang XR, Pfeiffer RM, Garcia-Closas M, Rimm DL, Lissowska J, Brinton LA, Peplonska B, Hewitt SM, Cartun RW, Mandich D, Sasano H, Evans DB, Sutter TR, Sherman ME.
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• [Journal Article] Significance of pathological evaluation for lymphatic vessel invasion in invasive breast cancer. (2007)
  • Author(s): Ito M, Moriya T, Ishida T, Usami S, Kasajima A, Sasano H, Ohuchi N.
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• [Journal Article] Metastin stimulates aldosterone synthesis in human adrenal cells. (2007)
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• [Presentation] 細胞診断学におけるバーチャルマイクロスコープの活用 (2007)
  • Author(s): 笹野公伸
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  • Year and Date: 20071130-1201
• [Presentation] 細胞診で悪性中皮腫を推定する-細胞形態からみた反応性中皮および肺腺癌との鑑別- (2007)
  • Author(s): 三浦弘守、渡辺みか、安達友津、田村聖月、石川 恵、安田奈津子、笹野公伸、森谷卓也
  • Organizer: 第46回日本臨床細胞学会秋期大会
  • Place of Presentation: 仙台国際センター(宮城)
  • Year and Date: 20071130-1201
• [Presentation] Pathological Analysis of Prognostic Markers in Gastroenteropacreatic tumor. (2007)
  • Author(s): Hironobu Sasano
  • Organizer: AFES2007 14th Congress of the ASEAN Federation of Endocrine Societies.
  • Place of Presentation: Kuala Lumpur Convention Center(Malaysia)
  • Year and Date: 20071129-1202
• [Presentation] Depelopment of Intracrinology and Its Manipulation. (2007)
  • Author(s): Hironobu Sasano.
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  • Year and Date: 20071109-10
• [Presentation] Sex steroids and human osteosarcroma -Hormone dependent cell proliferation. (2007)
  • Author(s): Osamu Dohi, Masahito Hatori, Takashi Suzuki, Katsuhiko Ono, Masami Hosaka, Jun-ichi Akahira, Yasuhiro Miki, Shunji Nagasaki, Hironobu Sasano.
  • Organizer: 66th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: PACIFICO YOKOHAMA(JAPAN)
  • Year and Date: 20071003-05
• [Presentation] The expression of estrogen receptor-related receptors in human epithelial ovarian cancer (2007)
  • Author(s): Jun-ichi Akahira, Takashi Suzuki, Fumihiko Suzuki, Ikumi Miura, Yasuhiro Miki, et. al.
  • Organizer: 66th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: PACIFICO YOKOHAMA(JAPAN)
  • Year and Date: 20071003-05
• [Presentation] Expression of midkine in human endometrium amd its disorder. (2007)
  • Author(s): Kojiro Tanabe, Mitsuyo Matsumoto, Jun-ichi Akahira, Takashi Suzuki, et. al.
  • Organizer: 66th Annual Meeting of Japanese Cancer Association Teamwork for Effective Reduction of Cancer
  • Place of Presentation: PACIFICO YOKOHAMA(JAPAN)
  • Year and Date: 20071003-05
• [Presentation] The possible role of 17beta-hydroxysteroid dehydrogenase type 12in Human breast cancer. (2007)
  • Author(s): Shunji Nagasaki, Yasuhiro Miki, Jun-ichi Akahira, Takashi Suzuki, and Hiroshi Handa, Hironobu Sasano.
  • Organizer: 66th Annual Meeting of Japanese Cancer Association
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  • Year and Date: 20071003-05
• [Presentation] ヒト上皮性卵巣癌におけるEstrogen receptor-related receptor(ERR)βの発現と臨床病理学的因子との関連について (2007)
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  • Organizer: 第80回日本内分泌学会学術総会
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• [Presentation] ヒト骨芽細胞における内分泌撹乱物質Bisphenol A の細胞増殖作用 (2007)
  • Author(s): 三木康宏、長崎修治、赤平純一、鈴木貴、笹野公伸.
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  • Year and Date: 20070614-0616
• [Presentation] 肺癌における組織内Estradiol濃度とEstrogen receptor発現の関係 (2007)
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• [Presentation] 副腎腫瘍におけるAdrenomedullin2/intermedin発現の検討 (2007)
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• [Presentation] 難治性副腎悪性腫瘍組織における標的治療因子の検索. (2007)
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  • Year and Date: 20070614-0616
• [Presentation] 前立腺癌におけるEstrogen Receptor β及びβcxの機能解析 (2007)
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  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 20070614-0616
• [Presentation] ヒト乳癌におけるEGR3(early growth response3)の発現意義. (2007)
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  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 20070614-0616
• [Presentation] The Expression of Estrogen beta Related Receptors in Human Epithelia Adenocarcinomal. (2007)
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• [Presentation] Early Growth Responsive Gene 3(EGR3)in Human Breast (2007)
  • Author(s): T. Suzuki, Y. Miki, T. Moriya, J. Akahira, T. Ishida, Y. Yamaguchi, S. Hayashiand H. Sasano.
  • Organizer: THE ENDOCRINE SOCIETY' S 89th Annual Meeting ENDO07.
  • Place of Presentation: TORONT
  • Year and Date: 20070602-0605
• [Presentation] 子宮内膜癌細胞におけるエストロゲン合成・代射酵素の発現〜 癌細胞のエストロゲン合成に対する間質細胞の影響〜 (2007)
  • Author(s): 宇都宮裕貴、伊藤潔、小林里香、高橋尚美、三木康宏、鈴木貴、本間誠次郎、林慎一and笹野公伸
  • Organizer: 第15回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 艮陸会館(宮城)
  • Year and Date: 2007-11-24
• [Presentation] 大腸癌におけるSteroid sulfataseとEstrogen sulfotransferaseの発現意義. (2007)
  • Author(s): 佐藤龍一郎、鈴木 貴、三木康宏、三浦 康、片寄 友、海野倫明、笹野公伸.
  • Organizer: 第15回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 艮陵会館(宮城)
  • Year and Date: 2007-11-24
• [Presentation] 骨芽細胞に対するSteroid and Xenobiotic Receptorを介したBisphenol Aの作用. (2007)
  • Author(s): 三木康宏、長崎修治、小野克彦、赤平純一、鈴木 貴、笹野公伸
  • Organizer: 第15回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 艮陵会館(宮城)
  • Year and Date: 2007-11-24
• [Presentation] 副腎皮質腫瘍組織における標的治療因子の免疫組織化学的検索 (2007)
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  • Place of Presentation: 艮陸会館(宮城)
  • Year and Date: 2007-11-24
• [Presentation] ヒト組織中ステロイドホルモン測定の臨床的病理的有用性. (2007)
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  • Year and Date: 2007-11-24
• [Presentation] ヒト上皮性卵巣癌におけるEstrogen receptor beta isoformsの発現についての検討 (2007)
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  • Year and Date: 2007-11-24
• [Presentation] 副腎皮質癌の病理診断の最近の進歩 (2007)
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  • Organizer: 第7回日本内分泌学会四国支部学術集会
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  • Year and Date: 2007-09-01