HER2/neu

HER2/neu
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1MFG、1MFL、1MW4、1N8Z、1QR1、1S78、2A91、2JWA、2KS1、2L4K、3BE1、3H3B、3N85、3PP0、3RCD、3MZW、3WLW、3WSQ、4GFU、4HRL、4HRM、4HRN、2N2A
识别号
别名	ERBB2；, CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1, erb-b2 receptor tyrosine kinase 2
外部ID	OMIM：164870 MGI：95410 HomoloGene：3273 GeneCards：ERBB2
EC number	2.7.10.1
相关疾病
	breast carcinoma、disease of cellular proliferation、非小细胞肺癌
为以下药物的标靶
	阿法替尼、canertinib、达科米替尼、拉帕替尼、mubritinib、来那替尼、玛格妥昔单抗、达科米替尼、帕妥珠单抗、图卡替尼、bms-599626、bms-690514、cp-724714、cudc-101、poziotinib、sapitinib、varlitinib、tesevatinib
基因位置（人类）
染色体	17号染色体
终止	39,730,426 bp
基因位置（小鼠）
染色体	小鼠11号染色体
终止	98,328,542 bp
RNA表达模式
	; ;
	查阅更多表达数据
基因本体
分子功能	• ErbB-3 class receptor binding; • 转移酶活性; • 核苷酸结合; • 蛋白激酶活性; • protein dimerization activity; • growth factor binding; • RNA polymerase I core binding; • 激酶活性; • protein C-terminus binding; • 血浆蛋白结合; • 相同蛋白质结合; • protein heterodimerization activity; • transmembrane receptor protein tyrosine kinase activity; • protein tyrosine kinase activity; • protein phosphatase binding; • ATP结合; • transmembrane signaling receptor activity; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • 酪氨酸激酶受体;
细胞组分	• integral component of membrane; • 膜; • myelin sheath; • receptor complex; • 细胞膜; • basolateral plasma membrane; • apical plasma membrane; • 细胞质的核周区域; • endosome membrane; • cytoplasmic vesicle; • 细胞核; • 细胞质; • 细胞质基质; • integral component of plasma membrane; • basal plasma membrane;
生物学过程	• positive regulation of protein phosphorylation; • peripheral nervous system development; • regulation of transcription, DNA-templated; • negative regulation of immature T cell proliferation in thymus; • positive regulation of MAP kinase activity; • 磷酸化; • transmembrane receptor protein tyrosine kinase signaling pathway; • positive regulation of epithelial cell proliferation; • cellular response to growth factor stimulus; • 伤口愈合; • oligodendrocyte differentiation; • regulation of angiogenesis; • positive regulation of translation; • transcription, DNA-templated; • 神经系统的发育; • MAPK cascade; • protein phosphorylation; • 心脏发育; • cell surface receptor signaling pathway; • positive regulation of GTPase activity; • positive regulation of cell growth; • regulation of microtubule-based process; • neuromuscular junction development; • regulation of ERK1 and ERK2 cascade; • 髓鞘形成; • 自体磷酸化; • phosphatidylinositol 3-kinase signaling; • positive regulation of transcription by RNA polymerase I; • 细胞增殖; • positive regulation of transcription by RNA polymerase III; • motor neuron axon guidance; • enzyme linked receptor protein signaling pathway; • 信号转导; • positive regulation of cell adhesion; • positive regulation of protein targeting to membrane; • ERBB2 signaling pathway; • phosphatidylinositol phosphate biosynthetic process; • positive regulation of gene expression; • peptidyl-tyrosine phosphorylation; • regulation of cell motility; • cellular response to epidermal growth factor stimulus; • regulation of transcription by RNA polymerase II; • negative regulation of ERBB signaling pathway; • positive regulation of protein kinase B signaling; • negative regulation of signal transduction; • 细胞分化; • negative regulation of apoptotic process; • positive regulation of ERK1 and ERK2 cascade; • intracellular signal transduction; • positive regulation of cell population proliferation; • neuron differentiation; • positive regulation of MAPK cascade;
	Sources:Amigo / QuickGO
直系同源
	2064
	13866
	ENSG00000141736
	ENSMUSG00000062312
	P04626
	P70424
	NM_001005862; NM_001289936; NM_001289937; NM_001289938; NM_004448
	NM_001003817; NM_010152
NP_001005862; NP_001276865; NP_001276866; NP_001276867; NP_004439;
	NP_001369711; NP_001369712; NP_001369713; NP_001369714; NP_001369715; NP_001369716; NP_001369717; NP_001369718; NP_001369719; NP_001369720; NP_001369721; NP_001369722; NP_001369723; NP_001369724; NP_001369725; NP_001369726; NP_001369727; NP_001369728; NP_001369729; NP_001369730; NP_001369731; NP_001369732; NP_001369733; NP_001369734; NP_001369735
	NP_001003817
	维基数据
查看/编辑人类	查看/编辑小鼠

人类表皮生长因子受体2（英语：human epidermal growth factor receptor 2，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转导途径，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。^[7]HER2基因是原癌基因，位于人类17号染色体长臂（17q21-q22）。^[8]

与癌症的关系

HER-2基因是影响乳癌预后的一个重要因素，大约有25%-30%左右的乳癌患者，受到体内癌细胞HER-2基因过量表现的影响，他们的癌细胞不仅繁殖能力强，对部分化学治疗药物也容易有抗药性，造成病患即使接受手术治疗，癌细胞仍然有较高复发及转移的几率，无法长期存活。

乳癌病患可分为Her-2/neu阳性或Her-2/neu阴性两种截然不同的预后之乳癌。乳癌患者的肿瘤，若HER-2蛋白质出现过量表现，这类的肿瘤生长速度较快且生物行为较为恶性，使得手术后复发率高于其他类型的乳癌。^[9]

针对HER2的药物

罗氏药厂开发的贺癌平（Herceptin）即是以HER2为标靶的药物，对晚期转移性的乳腺癌颇具效用。

重组型人源化单克隆抗体 Trastuzumab (Herceptin®), 是IgG1 monoclonal antibody，可透过结合到乳癌细胞膜上的HER2 receptor的Domain4去抑制下游的hetero- and homodimerization和信号传递。；
完全人源化单克隆抗体 Pertuzumab (Perjeta®)，和Trastuzumab药理作用位点相似，但Pertuzumab 是结合在HER2的Domain2，去抑制下游路径，而且因为Domain2是属于extracellular receptor dimerization，因此可防止其他的HER family members和HER2进行dimerization，从而抑制了ligand-induced signaling，抑制了细胞生长而进行细胞凋亡，其中HER2/HER3被认为是下游通路激活的最强二聚体；
单抗结合型药物 Ado-Trastuzumab emtansine (Kadcyla®)，为新药，是一种Antibody和Drug的conjugate（ADC）。Trastuzumab上述已介绍过他的作用位点，而新药T-DM1则是将Trastuzumab和maytansine 1用thioether键结起来，DM1即derivative of maytansine 1，是一种合成Microtubule 过程中dimerization的抑制剂，将Trastuzumab和cytotoxic agent DM1结合，除了有Trastuzumab本身能够与HER2 receptor Domain4结合，进而停止了癌细胞的生长，DM1透过receptor-mediated进入细胞内作用，并在lysosome内代谢，释放出含DM1的代谢产物，此物质可结合在Microtubule上，导致有丝分裂终止和细胞死亡。^[10]
Neratinib，为口服制剂，irreversible inhibitor，抑制HER2 and EGFR protein tyrosine kinase(TK)。^[11]
酪氨酸激酶抑制剂 Lapatinib Ditosylate (Tykerb®)，口服制剂，和Neratinib相似，一样是EGFR and HER2 tyrosine kinase的抑制剂。^[11]
mTOR 抑制剂 Everolimus (Afinitor®)

相互作用

参考文献

^ 與HER2/neu相關的疾病；在維基數據上查看/編輯參考.
^ 對人类表皮生长因子受体II起作用的藥物；在維基數據上查看/編輯參考.
^ ^3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000141736 - Ensembl, May 2017
^ ^4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000062312 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Olayioye MA. Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res. 2001, 3 (6): 385–389. PMID 11737890. doi:10.1186/bcr327.
^ Coussens L. Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu Oncogene. Science. 1985, 230: 1132–1139. doi:10.1126/science.2999974.
^ HER-2陽性早期乳癌治療的近況. 台湾癌症防治网. 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.
^ ^11.0 ^11.1 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; et al. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003, 8 (4): 307–25. PMID 12897328. doi:10.1634/theoncologist.8-4-307.
Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. 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; et al. Role of HER2/neu in tumor progression and therapy. 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; et al. Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy. World J. Gastroenterol. 2006, 12 (21): 3297–305. PMID 16733844.
Laudadio J, Quigley DI, Tubbs R, Wolff DJ. HER2 testing: a review of detection methodologies and their clinical performance. 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. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections. Cell Cycle. 2007, 6 (6): 643–6. PMID 17374991. doi:10.4161/cc.6.6.4033.
Del Bimbo A., Meoni M., Pala P. Accurate evaluation of HER-2 amplification in FISH images. 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

分类

[1] 與HER2/neu相關的疾病；在維基數據上查看/編輯參考.

[2] 對人类表皮生长因子受体II起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000141736 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000062312 - Ensembl, May 2017

[5] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[Olayioye_2001-7] Olayioye MA. Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res. 2001, 3 (6): 385–389. PMID 11737890. doi:10.1186/bcr327.

[Coussens_1985-8] Coussens L. Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu Oncogene. Science. 1985, 230: 1132–1139. doi:10.1126/science.2999974.

[9] HER-2陽性早期乳癌治療的近況. 台湾癌症防治网. 2009年10月16日 [2009-10-06]. （原始内容存档于2011年5月25日）.

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

[#1-11] 11.0 ^11.1 Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

HER2/neu

功能

与癌症的关系

针对HER2的药物

相互作用

参考文献

深入阅读

外部链接

Suggest as cover photo

Thank you for helping!

Install Wikiwand

Don't forget to rate us

Tell your friends about Wikiwand!

Enjoying Wikiwand?

Tell your friends and spread the love:

Your preferred languages

All languages

Follow Us

Don't forget to rate us

Our magic isn't perfect

Thank you for helping!

Oh no, there's been an error