Tacstd2-KO 基因敲除小鼠

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产品名称

Tacstd2-KO 基因敲除小鼠

产品编号

S-KO-10935

品系全称

C57BL/6JCya-Tacstd2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-56753-Tacstd2-B6J-VA

品系状态

使用本品系发表的文献需注明: Tacstd2-KO 基因敲除小鼠 mice (Strain S-KO-10935) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
tumor-associated calcium signal transducer 2
基因别称
EGP-1,GA733-1,Ly97,TROP2
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_020047 | Ensembl: ENSMUST00000058178
修饰方式
全身性基因敲除
靶向范围
Exon 1
敲除长度
~1.7 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:1861606Mice homozygous for a knock-out allele exhibit normal development, life expectancy and tumorigenesis. When combined with a Cdkn2a knock-out allele, mice exhibit increased incidence of induced spindle cell carcinoma and immortalized keratinocyte proliferation and migration.
TACSTD2,也称为Trophoblast Cell Surface Antigen 2 (TROP2),是一种跨膜糖蛋白,由Tacstd2基因编码。TROP2作为细胞内钙信号转导子,在多种癌症中差异性表达,并参与细胞自我更新、增殖、侵袭和存活等过程。研究表明,TROP2在许多正常组织中均有表达,但在多种癌症中过度表达,且其过度表达具有预后意义[2]。

在正常肝脏细胞中,TROP2在肝细胞、胆管细胞以及具有形成双能肝类器官潜力的TROP2int祖细胞群体中均有表达[1]。研究表明,TROP2基因表达在所有乳腺癌亚型中均可检测到,尤其在luminal A型和TNBC中表达较高,并与细胞上皮转化、粘附和增殖相关基因的表达呈正相关[3]。此外,在转移性去势抵抗性前列腺癌(mCRPC)中,TACSTD2基因在luminal和basal肿瘤中均有表达,但在神经内分泌前列腺癌中表达较低[4]。

在高级尿路上皮癌(aUC)中,TROP2/TACSTD2和NECTIN-4/NECTIN-4在蛋白质和转录水平上均有高度表达,且其表达状态与患者生存率无显著相关性[5]。在多种实体肿瘤中,TACSTD2基因表达与TP53、KRAS、ARID1A、FGFR3、CTNNB1等关键驱动基因的突变相关,且TACSTD2高表达的肿瘤患者总体生存期较短,免疫细胞浸润和T细胞炎症评分较高[6]。

此外,TACSTD2基因突变与胶状滴状角膜营养不良(GDLD)的发生相关[7]。TROP2靶向抗体药物偶联物(ADC)如sacituzumab govitecan(IMMU-132)已被批准用于治疗乳腺癌和尿路上皮癌,并在多种实体肿瘤中显示出显著的抗肿瘤活性[8]。此外,研究表明,TACSTD2可能是顺铂诱导的急性肾损伤(CP-AKI)的治疗靶点,药物如parthenolide、progesterone、premarin、estradiol和rosiglitazone等可能具有治疗CP-AKI的潜力[9]。

综上所述,TACSTD2/TROP2在多种癌症中表达异常,与肿瘤的发生、发展和预后密切相关。TROP2靶向ADCs如IMMU-132已在临床应用中显示出良好的疗效,为癌症治疗提供了新的策略。此外,TACSTD2在肝脏、角膜等正常组织中也发挥重要作用,其表达异常可能导致相关疾病的发生。深入研究TACSTD2的生物学功能和调控机制,将为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Aizarani, Nadim, Saviano, Antonio, Mailly, Laurent, Baumert, Thomas F, Grün, Dominic. 2019. A human liver cell atlas reveals heterogeneity and epithelial progenitors. In Nature, 572, 199-204. doi:10.1038/s41586-019-1373-2. https://pubmed.ncbi.nlm.nih.gov/31292543/
2. Shvartsur, Anna, Bonavida, Benjamin. . Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. In Genes & cancer, 6, 84-105. doi:. https://pubmed.ncbi.nlm.nih.gov/26000093/
3. Vidula, Neelima, Yau, Christina, Rugo, Hope. 2022. Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. In Breast cancer research and treatment, 194, 569-575. doi:10.1007/s10549-022-06660-x. https://pubmed.ncbi.nlm.nih.gov/35789445/
4. Sperger, Jamie M, Helzer, Kyle T, Stahlfeld, Charlotte N, Dehm, Scott M, Lang, Joshua M. . Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer. In Clinical cancer research : an official journal of the American Association for Cancer Research, 29, 2324-2335. doi:10.1158/1078-0432.CCR-22-1305. https://pubmed.ncbi.nlm.nih.gov/36939530/
5. Bahlinger, Veronika, Branz, Annalena, Strissel, Pamela L, Hartmann, Arndt, Eckstein, Markus. 2024. Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. In Histopathology, 84, 863-876. doi:10.1111/his.15130. https://pubmed.ncbi.nlm.nih.gov/38196202/
6. Morgenstern-Kaplan, Dan, Kareff, Samuel A, Trabolsi, Asaad, Vanderwalde, Ari M, Lopes, Gilberto. . Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors. In The oncologist, 29, e1480-e1491. doi:10.1093/oncolo/oyae168. https://pubmed.ncbi.nlm.nih.gov/38986529/
7. Alehabib, Elham, Jamshidi, Javad, Ghaedi, Hamid, Mohajerani, Fatemeh, Darvish, Hossein. 2017. Novel Mutations in TACSTD2 Gene in Families with Gelatinous Drop-like Corneal Dystrophy (GDLD). In International journal of molecular and cellular medicine, 6, 204-211. doi:10.22088/BUMS.6.4.204. https://pubmed.ncbi.nlm.nih.gov/29988226/
8. Cardillo, Thomas M, Govindan, Serengulam V, Sharkey, Robert M, Chang, Chien-Hsing, Goldenberg, David M. 2015. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. In Bioconjugate chemistry, 26, 919-31. doi:10.1021/acs.bioconjchem.5b00223. https://pubmed.ncbi.nlm.nih.gov/25915780/
9. Deng, Zebin, Dong, Zheng, Wang, Yinhuai, Liu, Jiachen, Deng, Fei. 2024. Identification of TACSTD2 as novel therapeutic targets for cisplatin-induced acute kidney injury by multi-omics data integration. In Human genetics, 143, 1061-1080. doi:10.1007/s00439-024-02641-w. https://pubmed.ncbi.nlm.nih.gov/38369676/