An epistatic interaction controls the latency of a transgene-induced mammary tumor

Voyer, Thomas Le; Lu, Zuliang; Babb, James S.; Lifsted, Traci; Williams, Max; Hunter, Kent W.

doi:10.1007/s003350010163

Cited by 49 publications

(31 citation statements)

References 27 publications

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“…The mouse model of mammary tumorigenesis induced by MMTV-pMT has been extensively used to examine pathways and molecules involved in mammary tumorigenesis and metastasis, including genetic loci (38,39), putative tumor suppressors (40,41), and other disease-modifying molecules (24,42,43). Our report is the first to investigate the role of Ron tyrosine kinase signaling in this mammary tumor and metastasis model.…”

Section: Discussionmentioning

confidence: 92%

Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

Peace¹,

Toney-Earley²,

Collins

et al. 2005

Cancer Research

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The tyrosine kinase receptor Ron has been implicated in several types of cancer, including overexpression in human breast cancer. This is the first report describing the effect of Ron signaling on tumorigenesis and metastasis in a mouse model of breast cancer. Mice with a targeted deletion of the Ron tyrosine kinase signaling domain (TKÀ/À) were crossed to mice expressing the polyoma virus middle T antigen (pMT) under the control of the mouse mammary tumor virus promoter. Both pMT-expressing wild-type control (pMT+/À TK+/+) and pMT+/À TKÀ/À mice developed mammary tumors and lung metastases. However, a significant decrease in mammary tumor initiation and growth was found in the pMT+/À TKÀ/À mice compared with controls. An examination of mammary tumors showed that there was a significant decrease in microvessel density, significantly decreased cellular proliferation, and a significant increase in terminal deoxynucleotidyl transferase-mediated nick end labelingpositive staining in mammary tumor cells from the pMT+/À TKÀ/À mice compared with the pMT+/À TK+/+ mice. Biochemical analyses on mammary tumor lysates showed that whereas both the pMT-expressing TK+/+ and TKÀ/À tumors have increased Ron expression compared with normal mammary glands, the pMT-expressing TKÀ/À tumors have deficits in mitogen-activated protein kinase and AKT activation. These results indicate that Ron signaling synergizes with pMT signaling to induce mammary tumor formation, growth, and metastasis. This effect may be mediated in part through the regulation of angiogenesis and through proliferative and cell survival pathways regulated by mitogen-activated protein kinase and AKT. (Cancer Res 2005; 65(4): 1285-93)

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Section: Discussionmentioning

confidence: 92%

Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

Peace¹,

Toney-Earley²,

Collins

et al. 2005

Cancer Research

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“…The biological significance of Cdc25A in the PyMT-transgenic mice has been studied recently. The epistatically interacting modifier loci in chromosomes 9 and 15 accelerate PyMT-induced mammary tumorigenesis in the I/LnJ background (33). Further analysis revealed that FVB/NJ chromosome 15 was associated with tumor acceleration and was conditioned on the presence of the I/LnJ allele on chromosome 9 (loci that have been designated as Apmt1 and Apmt2; ref.…”

Section: Discussionmentioning

confidence: 99%

Global Expression Profiling Identifies Signatures of Tumor Virulence in MMTV-PyMT-Transgenic Mice

et al. 2004

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“…Pooled protein samples were separated on SDS-PAGE pre-cast gels (Invitrogen Corp., Carlsbad, CA) then transferred to Immobilon-P membranes (Millipore). Western blotting was performed as previously described (14). The presence of the antigen was detected using an ECL-Plus Kit (Amersham) as per the manufacturer's protocol.…”

Section: Western Blotmentioning

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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An epistatic interaction controls the latency of a transgene-induced mammary tumor

Cited by 49 publications

References 27 publications

Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

Global Expression Profiling Identifies Signatures of Tumor Virulence in MMTV-PyMT-Transgenic Mice

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

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