特異的抗ヒトERβモノクローナル抗体PPZ0506発見がERβ研究に与えた衝撃
「1. 緒言」標的分子と特異的に結合する抗体は, 生命科学・医学分野で不可欠なツールであり, 様々な免疫学的測定法で使用される. 免疫組織化学染色法は, 生命科学・基礎医学分野では組織切片中の標的分子の発現・局在を同定する手法として, 組織病理学分野では病理組織検体内での標的マーカー分子の発現を評価することで診断手法として用いられる. 信頼性の高い免疫学的測定法の確立には, 使用する抗体の特異性が要となる. 特異性の高い抗体の存在は, 測定の再現性を高め, 該当する研究分野の発展に寄与する. しかし, 研究分野で普及している抗体が必ずしも抗原への特異性が保証されているわけではない. そのため,...
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| Published in | 日本医科大学医学会雑誌 Vol. 19; no. 4; pp. 332 - 338 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本医科大学医学会
25.12.2023
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| Online Access | Get full text |
| ISSN | 1349-8975 1880-2877 |
| DOI | 10.1272/manms.19.332 |
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| Abstract | 「1. 緒言」標的分子と特異的に結合する抗体は, 生命科学・医学分野で不可欠なツールであり, 様々な免疫学的測定法で使用される. 免疫組織化学染色法は, 生命科学・基礎医学分野では組織切片中の標的分子の発現・局在を同定する手法として, 組織病理学分野では病理組織検体内での標的マーカー分子の発現を評価することで診断手法として用いられる. 信頼性の高い免疫学的測定法の確立には, 使用する抗体の特異性が要となる. 特異性の高い抗体の存在は, 測定の再現性を高め, 該当する研究分野の発展に寄与する. しかし, 研究分野で普及している抗体が必ずしも抗原への特異性が保証されているわけではない. そのため, 非特異的な抗体の使用により, 研究の発展が阻害されることもありうる. ERβ研究は, まさに非特異的な抗体使用によって矛盾する結果が積み重なり, その発展が損なわれてきた1例である. これまで特異的抗ERβ抗体を作製・検索する試みがなされたが, 充分な特異性を持つ抗体を同定できずにいた. |
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| AbstractList | 「1. 緒言」標的分子と特異的に結合する抗体は, 生命科学・医学分野で不可欠なツールであり, 様々な免疫学的測定法で使用される. 免疫組織化学染色法は, 生命科学・基礎医学分野では組織切片中の標的分子の発現・局在を同定する手法として, 組織病理学分野では病理組織検体内での標的マーカー分子の発現を評価することで診断手法として用いられる. 信頼性の高い免疫学的測定法の確立には, 使用する抗体の特異性が要となる. 特異性の高い抗体の存在は, 測定の再現性を高め, 該当する研究分野の発展に寄与する. しかし, 研究分野で普及している抗体が必ずしも抗原への特異性が保証されているわけではない. そのため, 非特異的な抗体の使用により, 研究の発展が阻害されることもありうる. ERβ研究は, まさに非特異的な抗体使用によって矛盾する結果が積み重なり, その発展が損なわれてきた1例である. これまで特異的抗ERβ抗体を作製・検索する試みがなされたが, 充分な特異性を持つ抗体を同定できずにいた. |
| Author | 大塚, 真衣 松本, 恵介 小澤, 一史 小澤, 実那 肥後, 心平 石井, 寛高 服部, 裕次郎 森下, 雅大 |
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Warner M, Wu WF, Montanholi L, Nalvarte I, Antonson P, Gustafsson JA: Ventral prostate and mammary gland phenotype in mice with complete deletion of the ERβ gene. Proc Natl Acad Sci U S A 2020; 117: 4902-4909. 41. Gilad LA, Schwartz B: Association of estrogen receptor beta with plasma-membrane caveola components: implication in control of vitamin D receptor. J Mol Endocrinol 2007; 38: 603-618. 3. Macleod MR, Michie S, Roberts I, et al.: Biomedical research: increasing value, reducing waste. Lancet 2014; 383: 101-104. 45. Kanaya M, Higo S, Ozawa H: Neurochemical Characterization of Neurons Expressing Estrogen Receptor β in the Hypothalamic Nuclei of Rats Using in Situ Hybridization and Immunofluorescence. Int J Mol Sci 2019 Dec 23; 21: 115. https://doi.org/10.3390/ijms21010115 16. Hirata S, Shoda T, Kato J, Hoshi K: Isoform/variant mRNAs for sex steroid hormone receptors in humans. Trends Endocrinol Metab 2003; 14: 124-129. 34. 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Pasquali D, Staibano S, Prezioso D, et al.: Estrogen receptor beta expression in human prostate tissue. Mol Cell Endocrinol 2001; 178: 47-50. 44. Hattori Y, Ishii H, Tahara S, Morita A, Ozawa H: Accurate assessment of estrogen receptor profiles in non-functioning pituitary adenomas using RT-digital PCR and immunohistochemistry. Life Sci 2020; 260: 118416. https://doi.org/10.1016/j.lfs.2020.118416 23. Saunders PT, Fisher JS, Sharpe RM, Millar MR: Expression of oestrogen receptor beta (ER beta) occurs in multiple cell types, including some germ cells, in the rat testis. J Endocrinol 1998; 156: R13-R17. 32. Leav I, Lau KM, Adams JY, et al.: Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 2001; 159: 79-92. 42. Gittoes NJ, McCabe CJ, Sheppard MC, Franklyn JA: Estrogen receptor beta mRNA expression in normal and adenomatous pituitaries. 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Zhou Q, Nie R, Prins GS, Saunders PT, Katzenellenbogen BS, Hess RA: Localization of androgen and estrogen receptors in adult male mouse reproductive tract. J Androl 2002; 23: 870-881. |
| References_xml | – reference: 28. Critchley HO, Henderson TA, Kelly RW, et al.: Wild-type estrogen receptor (ERbeta1) and the splice variant (ERbetacx/beta2) are both expressed within the human endometrium throughout the normal menstrual cycle. J Clin Endocrinol Metab 2002; 87: 5265-5273. – reference: 8. Andersson S, Sundberg M, Pristovsek N, et al.: Insufficient antibody validation challenges oestrogen receptor beta research. Nat Commun 2017 Jun 15; 8: 15840. https://doi.org/10.1038/ncomms15840 – reference: 47. Langendonk M, de Jong MRW, Smit N, et al.: Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma. Blood Cancer J 2022 Mar 7; 12: 36. https://doi.org/10.1038/s41408-022-00631-7 – reference: 21. Pettersson K, Grandien K, Kuiper GG, Gustafsson JA: Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Mol Endocrinol 1997; 11: 1486-1496. – reference: 34. Wong NA, Malcomson RD, Jodrell DI, Groome NP, Harrison DJ, Saunders PT: ERbeta isoform expression in colorectal carcinoma: an in vivo and in vitro study of clinicopathological and molecular correlates. J Pathol 2005; 207: 53-60. – reference: 3. Macleod MR, Michie S, Roberts I, et al.: Biomedical research: increasing value, reducing waste. Lancet 2014; 383: 101-104. – reference: 36. Pasquali D, Rossi V, Esposito D, et al.: Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues. J Clin Endocrinol Metab 2001; 86: 2051-2055. – reference: 48. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS: Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology 1997; 138: 4613-4621. – reference: 35. Horvath LG, Henshall SM, Lee CS, et al.: Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res 2001; 61: 5331-5335. – reference: 25. Warner M, Wu WF, Montanholi L, Nalvarte I, Antonson P, Gustafsson JA: Ventral prostate and mammary gland phenotype in mice with complete deletion of the ERβ gene. Proc Natl Acad Sci U S A 2020; 117: 4902-4909. – reference: 9. Ishii H, Otsuka M, Kanaya M, Higo S, Hattori Y, Ozawa H: Applicability of anti-human estrogen receptor β antibody PPZ0506 for the immunodetection of rodent estrogen receptor β proteins. Int J Mol Sci 2019 Dec 13; 20: 6312. https://doi.org/10.3390/ijms20246312 – reference: 17. 石井, 寛高, 服部, 裕次郎, 小澤, 一史: エストロゲン受容体α遺伝子の5′-非翻訳領域の構造と発現制御. 日医大医会誌 2018; 14: 157-163. – reference: 23. Saunders PT, Fisher JS, Sharpe RM, Millar MR: Expression of oestrogen receptor beta (ER beta) occurs in multiple cell types, including some germ cells, in the rat testis. J Endocrinol 1998; 156: R13-R17. – reference: 45. Kanaya M, Higo S, Ozawa H: Neurochemical Characterization of Neurons Expressing Estrogen Receptor β in the Hypothalamic Nuclei of Rats Using in Situ Hybridization and Immunofluorescence. Int J Mol Sci 2019 Dec 23; 21: 115. https://doi.org/10.3390/ijms21010115 – reference: 38. Leygue E, Dotzlaw H, Lu B, Glor C, Watson PH, Murphy LC: Estrogen receptor beta: mine is longer than yours? J Clin Endocrinol Metab 1998; 83: 3754-3755. – reference: 31. Saunders PT, Millar MR, Williams K, et al.: Expression of oestrogen receptor beta (ERbeta1) protein in human breast cancer biopsies. Br J Cancer 2002; 86: 250-256. – reference: 22. Saunders PT, Maguire SM, Gaughan J, Millar MR: Expression of oestrogen receptor beta (ER beta) in multiple rat tissues visualised by immunohistochemistry. J Endocrinol 1997; 154: R13-R16. – reference: 26. Zhou Q, Nie R, Prins GS, Saunders PT, Katzenellenbogen BS, Hess RA: Localization of androgen and estrogen receptors in adult male mouse reproductive tract. J Androl 2002; 23: 870-881. – reference: 37. ペルセウスプロテオミクス: 抗ヒトERβマウスモノクローナル抗体 抗体仕様書; 2007. https://www.ppmx.com/img/SpecS_J_PPZ0506-00_ERb.pdf – reference: 11. Birgersson M, Katona B, Lindskog C, Pontén F, Williams C: Antibody validation for estrogen receptor beta. Methods Mol Biol 2022; 2418: 1-23. – reference: 15. Dahlman-Wright K, Cavailles V, Fuqua SA, et al.: International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev 2006; 58: 773-781. – reference: 32. Leav I, Lau KM, Adams JY, et al.: Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 2001; 159: 79-92. – reference: 2. Ioannidis JP: Why most published research findings are false. PLoS Med 2005 Aug 30; 2: e124. https://doi.org/10.1371/journal.pmed.0020124 – reference: 10. Hattori Y, Ishii H, Higo S, et al.: Optimization of immunohistochemical detection of rat ESR2 proteins with well-validated monoclonal antibody PPZ0506. Mol Cell Endocrinol 2021; 523: 111145. https://10.1016/j.mce.2020.111145 – reference: 12. Ozawa M, Hattori Y, Higo S, et al.: Optimized mouse-on-mouse immunohistochemical detection of mouse ESR2 proteins with PPZ0506 monoclonal antibody. Acta Histochem Cytochem 2022; 55: 159-168. – reference: 19. Mosselman S, Polman J, Dijkema R: ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996; 392: 49-53. – reference: 30. Saunders PT, Sharpe RM, Williams K, et al.: Differential expression of oestrogen receptor alpha and beta proteins in the testes and male reproductive system of human and non-human primates. Mol Hum Reprod 2001; 7: 227-236. – reference: 5. Skliris GP, Parkes AT, Limer JL, Burdall SE, Carder PJ, Speirs V: Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue. J Pathol 2002; 197: 155-162. – reference: 40. Yang SH, Liu R, Perez EJ, et al.: Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci U S A 2004; 101: 4130-4135. – reference: 43. Zhou W, Song Y, Xu H, et al.: In nonfunctional pituitary adenomas, estrogen receptors and slug contribute to development of invasiveness. J Clin Endocrinol Metab 2011; 96: E1237-E1245. – reference: 46. de Jong MRW, Visser L, Huls G, et al.: Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach. PLoS One 2018 Feb 28; 13: e0193098. https://doi.org/10.1371/journal.pone.0193098 – reference: 42. 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| Snippet | 「1. 緒言」標的分子と特異的に結合する抗体は, 生命科学・医学分野で不可欠なツールであり, 様々な免疫学的測定法で使用される. 免疫組織化学染色法は, 生命科学・基礎医学... |
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| Title | 特異的抗ヒトERβモノクローナル抗体PPZ0506発見がERβ研究に与えた衝撃 |
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