Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib.
Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib.
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使用MCF10A/MCF10CA1A乳腺癌进展细胞系模型来研究活性，突变形式的EGFR使用Gefitinib在乳腺癌发育和治疗中的影响。
DOI：
10.1371/journal.pone.0125232
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chenevix-Trench G
中科院分区：
文献类型：
--
作者：
Bessette DC;Tilch E;Seidens T;Quinn MC;Wiegmans AP;Shi W;Cocciardi S;McCart-Reed A;Saunus JM;Simpson PT;Grimmond SM;Lakhani SR;Khanna KK;Waddell N;Al-Ejeh F;Chenevix-Trench G
基底样和三阴性乳腺癌（TNBC）具有共同的分子特征、不良预后和向脑转移的倾向。表皮生长因子受体（EGFR）扩增发生在约50%的基底细胞样乳腺癌中，在高达约10%的亚洲TNBC患者中报告了表皮生长因子受体（EGFR）突变。在非小细胞肺癌中，EGFR酪氨酸激酶结构域中的几种不同突变赋予对受体酪氨酸激酶抑制剂的敏感性，但乳腺细胞中EGFR突变的致瘤潜力及其靶向治疗潜力尚不清楚。将含有EGFR的野生型、G719 S或E746-A750缺失突变体形式的构建体转染到MCF 10A乳腺细胞及其致瘤衍生物MCF 10 CA 1a中。研究了EGFR过表达和突变对增殖、迁移、侵袭、对吉非替尼的反应和体内肿瘤形成的影响。还进行了MCF 10A和MCF 10 CA 1a细胞系的拷贝数分析和全外显子组测序。突变型EGFR增加MCF 10A和MCF 10 CA 1a增殖和MCF 10A吉非替尼敏感性。EGFR-E746-A750缺失增加了MCF 10 CA 1a细胞的迁移和侵袭，并大大增加了MCF 10 CA 1a异种移植肿瘤的形成和生长。与MCF 10A细胞相比，MCF 10 CA 1a细胞在3号和9号染色体上表现出较大的增益区域，在7号染色体上表现出缺失，并且在许多与癌症有关的基因中表现出突变。突变EGFR增强MCF 10A细胞系的致癌特性，并增加对吉非替尼的敏感性。尽管EGFR E746-A750的添加使得MCF 10 CA 1a细胞在体内更具致瘤性，但其并不伴随吉非替尼敏感性的增加，这可能是由于MCF 10 CA 1a细胞系获得了额外的突变，包括PIK 3CA H1047 R突变。对TNBC/基底细胞样乳腺癌进行EGFR突变筛查可能有助于指导治疗，但与非小细胞肺癌一样，PIK 3CA中的伴随突变可能会导致吉非替尼耐药。
Basal-like and triple negative breast cancer (TNBC) share common molecular features, poor prognosis and a propensity for metastasis to the brain. Amplification of epidermal growth factor receptor (EGFR) occurs in ~50% of basal-like breast cancer, and mutations in the epidermal growth factor receptor (EGFR) have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung cancer several different mutations in the EGFR tyrosine kinase domain confer sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic potential of EGFR mutations in breast cells and their potential for targeted therapy is unknown. Constructs containing wild type, G719S or E746-A750 deletion mutant forms of EGFR were transfected into the MCF10A breast cells and their tumorigenic derivative, MCF10CA1a. The effects of EGFR over-expression and mutation on proliferation, migration, invasion, response to gefitinib, and tumour formation in vivo was investigated. Copy number analysis and whole exome sequencing of the MCF10A and MCF10CA1a cell lines were also performed. Mutant EGFR increased MCF10A and MCF10CA1a proliferation and MCF10A gefitinib sensitivity. The EGFR-E746-A750 deletion increased MCF10CA1a cell migration and invasion, and greatly increased MCF10CA1a xenograft tumour formation and growth. Compared to MCF10A cells, MCF10CA1a cells exhibited large regions of gain on chromosomes 3 and 9, deletion on chromosome 7, and mutations in many genes implicated in cancer. Mutant EGFR enhances the oncogenic properties of MCF10A cell line, and increases sensitivity to gefitinib. Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more tumourigenic in vivo it is not accompanied by increased gefitinib sensitivity, perhaps due to additional mutations, including the PIK3CA H1047R mutation, that the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for EGFR mutations may prove useful for directing therapy but, as in non-small cell lung cancer, accompanying mutations in PIK3CA may confer gefitinib resistance.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1186/bcr1636
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fulford LG;Reis-Filho JS;Ryder K;Jones C;Gillett CE;Hanby A;Easton D;Lakhani SR
通讯作者：
Lakhani SR
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
11.5
作者：
Duan, Zhenfeng;Zhang, Jianming;Hornicek, Francis J.
通讯作者：
Hornicek, Francis J.
影响因子：
6.4
作者：
Fulford, L. G.;Easton, D. F.;Hanby, A.
通讯作者：
Hanby, A.