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Controlled ErbB receptor dimerization

ABSTRACT: In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers. MCF10A-HER2-FKBP-HA cells were treated with AP1510, TGFalpha or heregulin for 48 hrs prior to RNA harvest for array analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Ritwik Ghosh

PROVIDER: E-GEOD-22288 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers.

Ghosh Ritwik R Narasanna Archana A Wang Shizhen Emily SE Liu Shuying S Chakrabarty Anindita A Balko Justin M JM González-Angulo Ana María AM Mills Gordon B GB Penuel Elicia E Winslow John J Sperinde Jeff J Dua Rajiv R Pidaparthi Sailaja S Mukherjee Ali A Leitzel Kim K Kostler Wolfgang J WJ Lipton Allan A Bates Michael M Arteaga Carlos L CL

Cancer research 20110215 5

In breast cancer cells with HER2 gene amplification, HER2 receptors exist on the cell surface as monomers, homodimers, and heterodimers with EGFR/HER3. The therapeutic antibody trastuzumab, an approved therapy for HER2(+) breast cancer, cannot block ligand-induced HER2 heterodimers, suggesting it cannot effectively inhibit HER2 signaling. Hence, HER2 oligomeric states may predict the odds of a clinical response to trastuzumab in HER2-driven tumors. To test this hypothesis, we generated nontransf ...[more]

PMID: 21324925

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