研究者総覧

坂本 隆子 (サカモト タカコ)

  • 環境予防医学講座 講師
Last Updated :2021/11/23

研究者情報

学位

  • 博士(医学)

ホームページURL

J-Global ID

研究キーワード

  • 植物エストロゲン   乳がん   腫瘍微小環境   レスベラトロール   エストロゲンレセプター   ホルモン依存性がん   エストロゲン   p53   細胞内情報伝達   

研究分野

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含まない
  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含む
  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含まない
  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含む
  • ライフサイエンス / 腫瘍生物学

経歴

  • 2005年09月 - 現在  自治医科大学医学部講師

研究活動情報

論文

  • Hyogo Horiguchi, Etsuko Oguma, Takako Sakamoto, Katsuyuki Murata, Fujio Kayama
    ARCHIVES OF TOXICOLOGY 88 1 137 - 144 2014年01月 [査読有り][通常論文]
     
    Diethylstilbestrol is an estrogenic endocrine disrupter that has diverse health effects in humans. Bisphenol A is another estrogen-like chemical with possible similar effects to diethylstilbestrol, which has been increasingly used for industry to lead to globally widespread human exposure to it. Hematopoiesis is another of their possible targets, since estrogen suppresses erythropoietin induction to induce anemia. The aim of this study was to clarify the effects of diethylstilbestrol and bisphenol A on erythropoietin induction in rats. We observed the effects of one-shot subcutaneous injection of diethylstilbestrol or bisphenol A on hypoxia-, bleeding-, and cobalt-stimulated erythropoietin induction within 24 h and the hematological outcomes after repeated subcutaneous injection of diethylstilbestrol three times a week for 1 month in rats. Diethylstilbestrol at 10-1,000 mu g/kg suppressed stimulus-elevated levels of plasma erythropoietin and its renal mRNA induction. In contrast, bisphenol A at 1,000 mu g/kg did not suppress plasma erythropoietin elevated by any stimuli. Repeated injection of diethylstilbestrol at 1,000 mu g/kg to rats for 1 month induced an anemic trend due to decelerated erythropoiesis through the insufficient production of erythropoietin, mimicking the effects of estradiol. In conclusion, diethylstilbestrol has a suppressive effect on erythropoietin induction, leading to deceleration of erythropoiesis and the development of anemia.
  • Takako Sakamoto, Hyogo Horiguchi, Etsuko Oguma, Fujio Kayama
    JOURNAL OF NUTRITIONAL BIOCHEMISTRY 21 9 856 - 864 2010年09月 [査読有り][通常論文]
     
    Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappa B-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17 beta-estradiol (E(2)) E(2) increased cell growth significantly, coumestrol Increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G(1)/S transition in cell cycle analysis, similar to E(2). This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-kappa B-dependent transcriptional activity On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) a silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ER alpha silencing abolished this reduction Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity (C) 2010 Elsevier Inc. All rights reserved
  • S Hayashi, T Sakamoto, A Inoue, N Yoshida, Y Omoto, Y Yamaguchi
    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 86 3-5 433 - 442 2003年09月 [査読無し][招待有り]
     
    Estrogen and its receptor play important roles in genesis and malignant progression of estrogen-dependent cancers, together with various growth factors. Functional cross-talk between estrogen-signaling and growth factor-mediated signaling pathways has been reported. Firstly, we show an example of the cross-talk that may alter the effect of antagonist on the breast and endometrial cancer cell growth. Our observations suggest that the constitutively activated MAP kinase-signaling pathway in endometrial cancer cells might enhance the transcriptional activity of ERalpha via phosphorylation of AF-1 domain. This mechanism may cause the growth stimulative effect of tamoxifen on the endometrium. Secondly, we show our recent study for comprehensive understanding of estrogen-signaling pathway using cDNA microarray. According to the results of the expression profiling of estrogen-responsive genes in ER-positive breast cancer cells using large-scale cDNA microarray, the custom-made cDNA microarray, on which only estrogen-responsive genes were loaded, was produced. Using this microarray consisting of the narrowed gene subset, we analyzed estrogen responsiveness of various cell lines and effect of estrogen antagonists. Aim of this study is not only to address the molecular mechanisms of estrogen-dependent growth of breast cancer, but also to develop the new diagnostic tools for responsiveness to hormone therapy of primary breast cancer patients. Finally, in order to understand the local tumor biology including stroma-cancer interaction, we recently developed the new analytical system using ERE-GFP introduced into breast cancer cells. Several observations indicated that these reporter cells were useful for assessment of stimulative effects of stroma cells adjacent to breast cancer on the estrogen- signaling pathway. These studies may provide not only new clues for elucidation of the molecular mechanisms of estrogen-dependent growth of breast cancer, but also assessment of anti-estrogen responses of individual breast cancer for patient-tailored hormone therapy. (C) 2003 Elsevier Ltd. All rights reserved.
  • T Sakamoto, H Eguchi, Y Omoto, T Ayabe, H Mori, S Hayashi
    MOLECULAR AND CELLULAR ENDOCRINOLOGY 192 1-2 93 - 104 2002年06月 [査読有り][通常論文]
     
    Tamoxifen is an estrogen receptor (ER)-antagonist that is widely used for the treatment of breast cancer, although it increases the risk of endometrial cancer. The mechanism mediating the stimulatory effect of tamoxifen on endometrial cancer is presently unknown. In this study we examined the effects of tamoxifen on Ishikawa 3H-12 endometrial cancer cells and MCF-7 breast cancer cells. Ishikawa cell growth was stimulated by 4-hydroxytamoxifen and accompanied by increased transcriptional activity of the endogenous ER. These stimulatory effects did not occur in MCF-7 cells. The relative transcriptional activity of the activation function (AF) I domain of ERalpha compared with that of the AF2 domain was 4-fold higher in Ishikawa cells than in MCF-7 cells, Mitogen-activated protein (MAP) kinase, which stimulates the transcriptional activity of AF1, was constitutively activated in Ishikawa cells, but not in MCF-7 cells. These observations suggest that the constitutively activated MAP kinase-signaling pathway in Ishikawa cells enhances the transcriptional activity of ERalpha via the AF1 domain. This ERalpha activation pathway may be involved in the stimulatory effect of tamoxifen on the development and/or progression of endometrial cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • T Sakamoto, T Murase, H Urushibata, K Kato, H Takada, T Imamura, H Mori, N Wake
    GYNECOLOGIC ONCOLOGY 71 1 53 - 58 1998年10月 [査読有り][通常論文]
     
    Recently, microsatellite instability (MI) has been demonstrated in some types of human cancers. In this study, we attempted to determine the frequency of MI in endometrial cancers and evaluate whether replication error (RER)-positive phenotype is correlated with known genetic mutations or the aberrations of other pathways in endometrial cancers. Seventy-two primary endometrial cancers were examined for microsatellite instability. Eleven tumors (15%) had RERs at two or more microsatellite loci, suggesting that generalized MI may be a molecular manifestation of endometrial cancers. We next examined whether the MI was associated with changes in the K-ras protooncogene, p53 tumor suppressor gene, and 18q LOH, which were frequently detected in endometrial cancers. The MI did not confer the potential to produce point mutations in the K-ras gene or 18q LOH, whereas the data were insufficient to identify the correlation between MI and p53 mutations in the cancers. These results suggest the presence of multiple mutation subsets that act in a complementary fashion in endometrial cancer development. (C) 1998 Academic Press.
  • Kato K, Sakamoto T, Wake N
    Oncology 55(Suppl 1) 41 - 48 1998年 [査読無し][招待有り]
  • T Sakamoto, N Nomura, H Mori, N Wake
    GYNECOLOGIC ONCOLOGY 63 2 173 - 179 1996年11月 [査読有り][通常論文]
     
    To define the target of chromosome 17p deletions, allelic losses in the 17p11.2 to 13.3 regions of 32 ovarian cancers were investigated. Twenty-one (68%) of 31 informative cancers had deletions on chromosome 17p. None of these 21 cancers involved deletions in the entire chromosome 17p even if deletions of a small chromosome region were infrequent, Of these 21, 17 cancers contained deletions at 17p13.1 or neighboring regions, The remaining 4 cancers with 17p deletions were uninformative for deletions at 17p13.1. Thus, most 17p deletions seemed to target the 17p13.1 region in ovarian cancers, Of the 30 ovarian cancers screened, 6 contained p53 mutations. One p53 allele was lost as a consequence of deletion and the other was mutated in 4 cancers, Seventeen cancers with deletions on 17p showed no evidence of p53 mutations, Thus, deletions on 17p that are common in ovarian cancers are not always accompanied by p53 gene mutations. (C) 1996 Academic Press, Inc.
  • Accumulation of genetic events in endometrial carcinoma and its cell growth inhibition by antisense oligonucleotide complementary to the mutated K-ras gene.
    Wake N, Gima T, Nishida J, Arima T, Imamura T, Nishida M, Kato K, Matsuda T, Tamura T, Hachiya T, Sakamoto T, Oshimura M
    Cancer Mol. Biol. 1 145 - 156 1994年 [査読無し][招待有り]
  • Tatsuo Yamamoto, Sachiko Yoshimura, Yukifumi Sasamori, Takako Sakamoto, Masahiro Ogino, Akira Kambegawa, Shouichi Okinaga, Kiyoshi Arai
    Asia‐Oceania Journal of Obstetrics and Gynaecology 18 2 177 - 185 1992年 [査読有り][通常論文]
     
    In order to investigate the renal change in preeclampsia, molecular weight and specific protein analyses in unconcentrated urine were performed by the immunoblot method. Urine samples were taken from 34 preeclamptic cases (pure type), including 20 severe cases. Polypeptide profiles of urine consisted of four patterns: low MW (L) pattern (tubular damage), high MW (H) pattern (glomerular damage), high and low MW (HL) pattern, and middle MW (M) pattern. The incidences of the HL, H, L, and M patterns were 26.5%, 14.7%, 11.8%, and 47.1%, respectively. The HL pattern was found more frequently in severe proteinuria than in mild proteinuria. High incidences of the HL and H patterns were found in the hypertensive group. Larger amounts of IgM, fibronection, IgG, and β2 microglobulin in urine were confirmed using specific antibodies. Our results suggest that the immunoblot method makes it possible to differentiate glomerular and tubular damages and to evaluate the severity of renal damage in preeclampsia using unconcentrated urine. © 1992 Japanese Society of Obstetrics and Gynaecology
  • M OGINO, T SAKAMOTO, T YAMAMOTO, H MORI, S OKINAGA, K ARAI
    GYNECOLOGIC ONCOLOGY 38 1 32 - 36 1990年07月 [査読有り][通常論文]

MISC

  • 坂本 隆子, 江口 英孝, 森 宏之, 林 慎一 ホルモンと臨牀 51 210 -214 2003年03月 [査読無し][通常論文]
  • 坂本 隆子, 荻野 雅弘, 山本 樹生, 森 宏之, 沖永 荘一, 園田 隆彦, 植田 国昭, 小尾 俊一, 小林 拓郎 日本産科婦人科學會雜誌 45 (5) 457 -463 1993年 [査読無し][通常論文]
     
    21例の上皮性卵巣癌症例 (漿液性13例, 粘液性3例, 類内膜癌2例, 明細胞癌3例) を対象に, がん抑制遺伝子p53および第17染色体の欠失を検討した. 同一症例から得た癌組織および正常組織から高分子量DNAを抽出し, Southern transfer後, 第17染色体短腕 (17p) 上に存在するがん抑制遺伝子p53又は第17染色体上の二つのVNTRプローブ (pYNZ22, pTHH59) とハイブリダイズさせ, 正常組織と癌組織のバンドを比較することで, ヘテロ接合性の消失 (loss of heterozygosity : LOH) を検出した. p53およびpYNZ22ではそれぞれ, 解析し得た14例中5例 (36%), 20例中9例 (45%) と高頻度のLOHが認められたが, pTHH59ではLOHは7例中1例 (14%) であつた. 以上の成績より, 上皮性卵巣癌の発生・進展にはp53の欠失が関与する例があることが示唆された.
  • 坂本 隆子, 荻野 雅弘, 山本 樹生, 森 宏之, 沖永 荘一, 荒井 清 日本産科婦人科學會雜誌 42 (5) 415 -421 1990年 [査読無し][通常論文]
     
    マウス腫瘍2株(M-5076細網肉腫, MH-134肝癌)を用いて液体試料の腹水による制癌剤感受性試験(Subrenal Capsule Assay : SRCA)の基礎的検討を行った. 腹水は4℃に静置, 腫瘍細胞を沈澱させるとゼリー状のclotが形成された. これを約1mm^3の大きさに細切, 一部を取ってトリパンブルー液に溶解して腫瘍細胞の生存率を計測した後, 残りをマウスの腎被膜下に移植した. 移植後6日目にマウスを屠殺して腫瘍径の増殖値および組織学的所見について検討したところ以下の成績を得た. (1)腹水静置後1〜2日で再現性よくclotが形成され, 含有腫瘍細胞の生存率はM-5076で79.9±11.0%, MH-134で90.1±5.9%といずれも高値を示した. (2)腹水試料移植6日目の腎被膜下の腫瘍増殖は両腫瘍とも対照群で著しく, 制癌剤投与群では単剤投与群>二剤併用群>三剤併用群の順で有意に(p<0.05〜0.005)縮小した. (3)腹水試料の腫瘍のSRCAにおける増殖は対照群, 薬剤投与群とも固形腫瘍の増殖よりも良好であった. また腹水試料の増殖値と固形腫瘍の増殖値とを比較すると, M-5076はr=0.93, MH-134はr=0.64と高い相関が認められた. (4)組織学的検討を行った結果両腫瘍とも腫瘍細胞の増生が認められ, 腫瘍は腎被膜下に平面的に広がるように増殖していた. 以上の結果より腹水も固形腫瘍と同様SRCAに有用な試料となりうることが示された.


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