HER2/neu

Erb-b2 receptor tyrosine kinase 2
	PDB繪製基於1n8z 曲妥珠單抗Fab片段(藍色)結合到HER2(米色)的胞外域。
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1MFG, 1MFL, 1MW4, 1N8Z, 1QR1, 1S78, 2A91, 2JWA, 2KS1, 2L4K, 3BE1, 3H3B, 3MZW, 3N85, 3PP0, 3RCD
标识
代号	ERBB2; CD340; HER-2; HER-2/neu; HER2; MLN 19; NEU; NGL; TKR1
扩展标识	遗传学：164870 鼠基因：95410 同源基因：3273 ChEMBL: 1824 GeneCards: ERBB2 Gene
EC編號	2.7.10.1
基因本体论描述
分子功能	· RNA polymerase I core binding; · protein tyrosine kinase activity; · transmembrane receptor protein tyrosine kinase activity; · receptor signaling protein tyrosine kinase activity; · transmembrane signaling receptor activity; · epidermal growth factor-activated receptor activity; · protein binding; · ATP binding; · protein C-terminus binding; · growth factor binding; · protein phosphatase binding; · identical protein binding; · ErbB-3 class receptor binding; · protein heterodimerization activity; · protein dimerization activity;
细胞成分	· nucleus; · plasma membrane; · endosome membrane; · integral to membrane; · basolateral plasma membrane; · apical plasma membrane; · receptor complex; · perinuclear region of cytoplasm;
生物过程	· positive regulation of protein phosphorylation; · transcription, DNA-dependent; · protein phosphorylation; · signal transduction; · cell surface receptor signaling pathway; · enzyme linked receptor protein signaling pathway; · transmembrane receptor protein tyrosine kinase signaling pathway; · epidermal growth factor receptor signaling pathway; · nervous system development; · axon guidance; · peripheral nervous system development; · heart development; · neuromuscular junction development; · motor neuron axon guidance; · cell proliferation; · fibroblast growth factor receptor signaling pathway; · phosphatidylinositol 3-kinase cascade; · signal transduction by phosphorylation; · positive regulation of cell growth; · mammary gland development; · positive regulation of Rho GTPase activity; · regulation of microtubule-based process; · negative regulation of immature T cell proliferation in thymus; · wound healing; · myelination; · positive regulation of MAP kinase activity; · innate immune response; · positive regulation of translation; · regulation of angiogenesis; · positive regulation of cell adhesion; · positive regulation of transcription from RNA polymerase I promoter; · positive regulation of transcription from RNA polymerase III promoter; · protein autophosphorylation; · neurotrophin TRK receptor signaling pathway; · phosphatidylinositol-mediated signaling; · positive regulation of epithelial cell proliferation; · regulation of ERK1 and ERK2 cascade;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体

人类表皮生长因子受体2（英語：，缩写为HER2，亦称为Neu、ErbB-2、CD340（分化群340）或p185）是一种由ERBB2基因编码的蛋白质。HER2是表皮生长因子受体（EGFR/ErbB）家族的成员。

功能

HER2是结合在细胞膜表面的受体酪氨酸激酶，参与导致细胞生长和分化的信号传导途径，由原癌基因HER2/neu编码。一般认为HER2是一个孤受体，表皮生长因子家族的配体都不能激活它。但配体结合ErbB受体时可形成二聚体，且HER2可与ErbB家族的其他成员结合成异二聚体。[1]HER2基因是原癌基因，位于人类第17号染色体长臂（17q21-q22）。[2]

與癌症的關係

HER-2基因是影響乳癌預後的一個重要因素，大約有25%-30%左右的乳癌患者，受到體內癌細胞HER-2基因過量表現的影響，他們的癌細胞不僅繁殖能力強，對部份化學治療藥物也容易有抗藥性，造成病患即使接受手術治療，癌細胞仍然有較高復發及轉移的機率，無法長期存活。

乳癌病患可分為Her-2/neu陽性或Her-2/neu陰性兩種截然不同的預後之乳癌。乳癌患者的腫瘤，若HER-2蛋白質出現過量表現，這類的腫瘤生長速度較快且生物行為較為惡性，使得手術後復發率高於其他類型的乳癌。[3]

表皮生長因子受體(EGFR)信號傳導級聯

針对HER2的葯物

羅氏藥廠開發的賀癌平（Herceptin）即是以HER2為标靶的葯物，對晚期转移性的乳腺癌頗具效用。

1. 重组型人源化单克隆抗体 Trastuzumab (Herceptin®), 是IgG1 monoclonal antibody，可透過結合到乳癌細胞膜上的HER2 receptor的Domain4去抑制下游的hetero- and homodimerization和信號傳遞。； 2. 完全人源化单克隆抗体 Pertuzumab (Perjeta®)，和Trastuzumab藥理作用位點相似，但Pertuzumab 是結合在HER2的Domain2，去抑制下游路徑，而且因為Domain2是屬於extracellular receptor dimerization，因此可防止其他的HER family members和HER2進行dimerization，從而抑制了ligand-induced signaling，抑制了細胞生長而進行細胞凋亡，其中HER2/HER3被认为是下游通路激活的最强二聚体； 3. 单抗结合型药物 Ado-Trastuzumab emtansine (Kadcyla®)，為新藥，是一種Antibody和Drug的conjugate（ADC）。Trastuzumab上述已介紹過他的作用位點，而新藥T-DM1則是將Trastuzumab和maytansine 1用thioether鍵結起來，DM1即derivative of maytansine 1，是一種合成Microtubule 過程中dimerization的抑制劑，將Trastuzumab和cytotoxic agent DM1結合，除了有Trastuzumab本身能夠與HER2 receptor Domain4結合，進而停止了癌細胞的生長，DM1透過receptor-mediated進入細胞內作用，並在lysosome內代謝，釋放出含DM1的代謝產物，此物質可結合在Microtubule上，導致有絲分裂終止和細胞死亡。[4] 4. Neratinib，為口服製劑，irreversible inhibitor，抑制HER2 and EGFR protein tyrosine kinase(TK)。[5] 5. 酪氨酸激酶抑制剂 Lapatinib Ditosylate (Tykerb®)，口服製劑，和Neratinib相似，一樣是EGFR and HER2 tyrosine kinase的抑制劑。[6] 6. mTOR 抑制剂 Everolimus (Afinitor®)

参考文献

Olayioye MA. . Breast Cancer Res. 2001, 3 (6): 385–389. PMID 11737890. doi:10.1186/bcr327.
Coussens L. . Science. 1985, 230: 1132–1139. doi:10.1126/science.2999974.
. 台灣癌症防治網. 2009年10月16日 [2009-10-06]. （原始内容存档于2011年5月25日）.
Sadeghi, S., Olevsky, O., & Hurvitz, S. A. (2014). Profiling and targeting HER2-positive breast cancer using trastuzumab emtansine. Pharmacogenomics and personalized medicine, 7, 329.
Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208
Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208

深入阅读

Ross JS, Fletcher JA, Linette GP; 等. . Oncologist. 2003, 8 (4): 307–25. PMID 12897328. doi:10.1634/theoncologist.8-4-307.
Zhou BP, Hung MC. . Semin. Oncol. 2003, 30 (5 Suppl 16): 38–48. PMID 14613025. doi:10.1053/j.seminoncol.2003.08.006.
Ménard S, Casalini P, Campiglio M; 等. . Cell. Mol. Life Sci. 2005, 61 (23): 2965–78. PMID 15583858. doi:10.1007/s00018-004-4277-7.
Becker JC, Muller-Tidow C, Serve H; 等. . World J. Gastroenterol. 2006, 12 (21): 3297–305. PMID 16733844.
Laudadio J, Quigley DI, Tubbs R, Wolff DJ. . Expert Rev. Mol. Diagn. 2007, 7 (1): 53–64. PMID 17187484. doi:10.1586/14737159.7.1.53.
Bianchi F, Tagliabue E, Ménard S, Campiglio M. . Cell Cycle. 2007, 6 (6): 643–6. PMID 17374991. doi:10.4161/cc.6.6.4033.
Del Bimbo A., Meoni M., Pala P. . Imaging Systems and Techniques (IST), 2010 IEEE International Conference on. 2010: 407–10. ISBN 978-1-4244-6492-0. doi:10.1109/IST.2010.5548461.

外部链接

ERBB2 expression across human cancerous and healthy tissues
AACR Cancer Concepts Factsheet on HER2
Her2/neu Vaccine Protects Against Tumor Growth
Chimeric molecules and Methods of Use
Breast Friends for Life Network - A South African Breast Cancer Support Forum for HER2 Positive Women
MeSH（醫學主題詞）上面的Receptor,+erbB-2（美式英语）

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[Olayioye_2001-1] Olayioye MA. . Breast Cancer Res. 2001, 3 (6): 385–389. PMID 11737890. doi:10.1186/bcr327.

[Coussens_1985-2] Coussens L. . Science. 1985, 230: 1132–1139. doi:10.1126/science.2999974.

[3] . 台灣癌症防治網. 2009年10月16日 [2009-10-06]. （原始内容存档于2011年5月25日）.

[4] Sadeghi, S., Olevsky, O., & Hurvitz, S. A. (2014). Profiling and targeting HER2-positive breast cancer using trastuzumab emtansine. Pharmacogenomics and personalized medicine, 7, 329.

[5] Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208

[6] Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208