HER-2 Signaling, Acquisition of Growth Factor Independence, and Regulation of Biological Networks Associated with Cell Transformation

被引：13

作者：

Bollig-Fischer, Aliccia ^{[1
]}

Dziubinski, Michele ^{[1
]}

Boyer, Alaina ^{[1
]}

Haddad, Ramsi ^{[1
]}

Giroux, Craig N. ^{[1
]}

Ethier, Stephen P. ^{[1
]}

机构：

[1] Wayne State Univ, Sch Med, Karmanos Canc Inst, Breast Canc Biol Program, Detroit, MI 48201 USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 20期

关键词：

MAMMARY EPITHELIAL-CELLS; HUMAN BREAST-CANCER; DIFFERENTIATION FACTOR HEREGULIN; CARCINOMA CELLS; TYROSINE KINASE; FACTOR RECEPTOR; FACTOR-I; EXPRESSION; OVEREXPRESSION; PROLIFERATION;

D O I：

10.1158/0008-5472.CAN-10-1529

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Activated oncogenes are the dominant drivers of malignant progression in human cancer, yet little is known about how the transformation from proto-oncogene to activated oncogene drives the expression of transformed phenotypes. An isogenic model of HER-2-mediated transformation of human mammary epithelial cells was used along with HER-2-amplified human breast cancers to investigate how HER-2 activation alters its properties as a signaling molecule and changes the networks of HER-2-regulated genes. Our results show that full oncogenic activation of HER-2 is the result of a transition in which activated HER-2 acquires dominant signaling properties that qualitatively alter the network of genes regulated by the activated oncogene compared with the proto-oncogene. Consequently, gene expression programs related to invasion, cell stress, and stemness become regulated by HER-2 in a manner not observed in nontransformed cells, even when HER-2 is overexpressed. Our results offer novel insights into biological processes that come under the control of HER-2 after it acquires full oncogenic potential. Cancer Res; 70( 20); 7862-73. (C) 2010 AACR.

引用

页码：7862 / 7873

页数：12

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