Proteomic and phosphoproteomic alterations in benign, premalignant and tumor human breast epithelial cells and xenograft lesions: biomarkers of progression.
Proteomic and phosphoproteomic alterations in benign, premalignant and tumor human breast epithelial cells and xenograft lesions: biomarkers of progression.
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DOI：
10.1002/ijc.24278
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Novak, Raymond F.
中科院分区：
文献类型：
--
作者：
Kim, So Hee;Miller, Fred R.;Tait, Larry;Zheng, Jie;Novak, Raymond F.
MCF 10A人乳腺上皮细胞谱系包括良性MCF 10A细胞、癌前细胞（MCF 10AT、MCF 10ATG 3B）和恶性MCF 10 CA 1a肿瘤细胞。癌前病变和肿瘤细胞概括了与PBD和癌的时间发展相关的进行性变化。Ras蛋白水平在10AT、10ATG 3B和10 CA 1a细胞中分别升高6.9、22.4和32.2倍。K-Ras未检测到，N-Ras水平无变化; 10 CA 1a肿瘤细胞中Rac和Rho水平升高。磷酸-磷脂酰肌醇3-激酶、磷酸肌醇依赖性蛋白激酶1（PDK 1）、磷酸-PDK 1、磷酸-真核翻译起始因子4 E（eIF 4 E）和磷酸-真核起始因子4 E结合蛋白1（4 E-BP 1）水平在细胞谱系中逐渐增加，在10 CA 1a肿瘤细胞中监测到最大增加。相对于10A细胞，10 CA 1a细胞中磷酸化Ser 473和Thr 408 Akt水平分别增加了10.2倍和136倍。相对于10A细胞，10 CA 1a细胞中磷酸-p70 S6激酶（p70 S6 K）增加> 2倍。免疫组化证实Ras，磷酸化Akt和磷酸化p70 S6 K（Thr 421/Ser 424）表达的病变所产生的癌前病变和肿瘤细胞。FOXO 1、磷酸化FOXO 1和磷酸化FOXO 4在10ATG 3B癌前和10 CA 1a肿瘤细胞中显著升高。磷酸化FOXO 3a逐渐升高，在10 CA 1a肿瘤细胞中检测到最高水平。免疫组化显示，磷酸化FOXO 1，3a和4染色在良性病变中较少，但在晚期10ATG 3B和恶性10 CA 1a病变中升高，显示细胞和病变之间的对应关系。因此，磷酸化-Akt和磷酸化-FOXO 1、3a和4值得考虑作为来自增生性乳腺组织的致瘤风险的生物标志物。
The MCF10A human breast epithelial cell lineage includes the benign MCF10A cells, premalignant cells (MCF10AT, MCF10ATG3B) and malignant MCF10CA1a tumor cells. The premalignant and tumor cells recapitulate the progressive alterations associated with the temporal development of PBD and carcinoma. Ras protein levels were elevated 6.9-, 22.4- and 32.2-fold in 10AT, 10ATG3B and 10CA1a cells respectively, relative to 10A cells. K-Ras was not detected, N-Ras levels were unchanged; Rac and Rho levels increased in 10CA1a tumor cells. Phospho-phosphatidylinositol 3-kinase, phosphoinositide-dependent protein kinase 1 (PDK1), phospho-PDK1, phospho-eukaryotic translation initiation factor 4E (eIF4E) and phospho-eukaryotic initiation factor 4E binding protein 1 (4E-BP1) levels progressively increased in the cell lineage, with the greatest increase monitored in 10CA1a tumor cells. Phospho Ser 473 and Thr 408 Akt levels increased 10.2- and 136-fold in 10CA1a cells, respectively, relative to 10A cells. Phospho- p70S6 kinase (p70S6K) increased > 2-fold in 10CA1a cells, relative to 10A cells. Immunohistochemistry confirmed Ras, phospho-Akt and phospho-p70S6K (Thr 421/Ser 424) expression in lesions arising from premalignant and tumor cells. FOXO 1, phospho-FOXO 1 and phospho-FOXO 4 were significantly elevated in 10ATG3B premalignant and 10CA1a tumor cells. Phospho-FOXO 3a was progressively elevated, with the greatest levels detected in 10CA1a tumor cells. Immunohistochemistry revealed that phospho-FOXO 1, 3a and 4 staining was less in benign lesions, but elevated in advanced 10ATG3B and malignant 10CA1a lesions, showing a correspondence between the cells and lesions. Hence, phospho-Akt and phospho-FOXO 1, 3a and 4 merit consideration as biomarkers of tumorigenic risk from hyperplastic breast tissue.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
6.4
作者：
DEBIASI, F;DELSAL, G;HAND, PH
通讯作者：
HAND, PH
DOI：
10.1073/pnas.87.21.8212
发表时间：
1990-11-01
影响因子：
11.1
作者：
DEBENEDETTI, A;RHOADS, RE
通讯作者：
RHOADS, RE
影响因子：
56.9
作者：
Dennis, PB;Jaeschke, A;Thomas, G
通讯作者：
Thomas, G
影响因子：
254.7
作者：
Jemal, A;Tiwari, RC;Thun, MJ
通讯作者：
Thun, MJ