In:
Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 10_Supplement ( 2013-10-01), p. A092-A092
Abstract:
Accumulating evidence indicates that tumor cells spread to distant sites much earlier than previously thought. The analysis of the BALB-neuT transgenic mouse model of breast cancer revealed that the relative number of disseminating cancer cells is highest at early stages of tumorigenesis. To unravel the mechanisms of early dissemination we performed a stage-dependent analysis of gene expression patterns in BALB-neuT mice. At the stage of atypical hyperplasia (ADH) gene expression profiles differed substantially from advanced tumors and lung metastases. We identified an ADH-specific gene expression signature and found that among the several hundred differentially expressed genes, many of them are regulated by sex hormones. We investigated whether this expression pattern might be linked to the propensity to disseminate. For this we established a surrogate signature for the ADH-specific pattern comprising five genes and tracked the regulating role of hormones in vitro or in vivo. Our results indicate that sex hormones act indirectly on mammary stem and progenitor cells to induce dissemination and metastasis and that hormone nuclear receptors are down-regulated in advanced tumors. Thereby, large tumors become less capable of disseminating metastatic cells. Citation Format: Hedayatollah Hosseini, Lahiri Kanth Nanduri, Carolin Ehrl, Matthias Maneck, Yves Husemann, Christoph A. Klein. Molecular mechanisms of early metastatic dissemination in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A092.
Type of Medium:
Online Resource
ISSN:
1541-7786
,
1557-3125
DOI:
10.1158/1557-3125.ADVBC-A092
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2097884-4
SSG:
12
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