Signal transduction in mammary tumorigenesis: a transgenic perspective

Dankort, David; Muller, William J.

doi:10.1038/sj.onc.1203272

Cited by 88 publications

(65 citation statements)

References 110 publications

(87 reference statements)

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“…Expression of wild type Neu or constitutively active Neu or ErbB-2 alleles in the mammary epithelia of transgenic mice results in the induction of metastatic mammary tumors (reviewed in Ref. 5). Taken together, these data suggest that activation of ErbB-2/Neu plays a causal role in mammary tumorigenesis.…”

mentioning

confidence: 52%

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins

Dankort

Jeyabalan

Jones

et al. 2001

Journal of Biological Chemistry

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mentioning

confidence: 52%

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins

Dankort

Jeyabalan

Jones

et al. 2001

Journal of Biological Chemistry

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“…ErbB-2 (HER2/Neu), a member of the epidermal growth factor receptor tyrosine kinase family, is overexpressed in B30% of primary human breast cancers (reviewed Mansour et al, 1994;Dankort and Muller, 2000). It is also believed that HER2 overexpression leads to an aggressive tumor phenotype as high levels of HER2 expression are observed in many invasive human ductal carcinomas, but rarely observed in benign breast disorders.…”

Section: Introductionmentioning

confidence: 99%

The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility

Kristin¹,

Wagner

Storbeck³

et al. 2009

Oncogene

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The Ste20-like kinase, SLK, is involved in the control of cell motility through its effects on actin reorganization and focal adhesion turnover. Here we investigated the role of SLK in chemotaxis downstream of the tyrosine kinase receptor, HER2/ErbB2/Neu, which is frequently overexpressed in human breast cancers. Our results show that SLK is required for the efficient cell migration of human and mouse mammary epithelial cell lines in the presence of the Neu activator, heregulin, as a chemoattractant. SLK activity is stimulated by heregulin treatment or by overexpression of activated Neu. Phosphorylation of tyrosine 1201 or tyrosines 1226/7 on Neu is a key event for SLK activation and cell migration, and cancer cell invasion mediated by these tyrosines is inhibited by kinase-inactive SLK. Signaling pathway inhibitors show that Neu-mediated SLK activation is dependent on MEK, PI3K, PLCc and Shc signaling. Furthermore, heregulinstimulated SLK activity requires signals from the focal adhesion proteins, FAK and src. Finally, phospho-FAK analysis shows that SLK is required for Neu-dependent focal adhesion turnover. Together, these studies define an interaction between Neu and SLK signaling in the regulation of cancer cell motility.

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“…In addition, a core interaction network revolving around H-Ras, Grb2, and Egfr (shown in Figure 3) was identified in mice treated with caffeine at the age of 60 days, with the majority of proteins in the network participating in the regulation of Akt phosphorylation or/ and cell proliferation. Since the Akt signaling pathway is part of active oncogenic pathways initiated by the PyMT antigen (25), the effect of caffeine on this pathway may be related to its inhibition of tumor dissemination. Similarly, the association network assembled from proteins differentially regulated by DBA/2J allele shows that activation of Stat proteins and apoptosis pathways may be potentially related to its metastatic suppression mechanism.…”

Section: Biological Association Network (Ban) Analysismentioning

confidence: 99%

Parallel Analysis of Transcript and Translation Profiles: Identification of Metastasis-Related Signal Pathways Differentially Regulated by Drug and Genetic Modifications

Yang¹,

Yu²,

Yi³

et al. 2006

J. Proteome Res.

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Tumor metastasis is a complex multi-step process normally involving dysregulation of multiple signal transduction pathways. In this study we developed a novel approach to efficiently define dysreguated pathways associated with metastasis by comparing global gene and protein expressions of two distinct metastasis-suppressed models. Consequently, we identified common features shared by the two models which are potentially associated with metastasis.The efficiency of metastasis from the highly aggressive polyoma middle T-induced mouse mammary tumors was suppressed by either prolonged caffeine exposure or by breeding the animal to a low metastastic mouse strain. Molecular profiles of the primary tumors from both metastasis-suppressed classes were then derived to identify molecules and pathways that might underlie a common mechanism of metastasis. A number of differentially regulated genes and proteins were identified, including genes encoding basement membrane components, which were inversely related to metastatic efficiency. In addition, the analysis revealed that the Stat signal transduction pathways were potentially associated with metastasis inhibition, as demonstrated by enhanced Stat1 activation, and decreased Stat5 phosphorylation in both genetic and pharmacological modification models. Tumor cells of low-metastatic genotypes also demonstrated anti-apoptotic properties. The common changes of these pathways in all of the metastasis-suppressed systems suggest that they may be critical components in the metastatic cascade, at least in this model system. Our data demonstrate that analysis of common changes in genes and proteins in a metastatic-related context greatly decrease the complexity of data analysis, and may serve as a screening tool to identify biological important factors from large scale data.

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Signal transduction in mammary tumorigenesis: a transgenic perspective

Cited by 88 publications

References 110 publications

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins

The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility

Parallel Analysis of Transcript and Translation Profiles: Identification of Metastasis-Related Signal Pathways Differentially Regulated by Drug and Genetic Modifications

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