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J Biol Chem. 2010 Mar 12;285(11):8218-26. doi: 10.1074/jbc.M110.100792. Epub 2010 Jan 6.

c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion.

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1
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Abstract

The molecular mechanisms governing breast tumor cellular self-renewal contribute to breast cancer progression and therapeutic resistance. The ErbB2 oncogene is overexpressed in approximately 30% of human breast cancers. c-Jun, the first cellular proto-oncogene, is overexpressed in human breast cancer. However, the role of endogenous c-Jun in mammary tumor progression is unknown. Herein, transgenic mice expressing the mammary gland-targeted ErbB2 oncogene were crossed with c-jun(f/f) transgenic mice to determine the role of endogenous c-Jun in mammary tumor invasion and stem cell function. The excision of c-jun by Cre recombinase reduced cellular migration, invasion, and mammosphere formation of ErbB2-induced mammary tumors. Proteomic analysis identified a subset of secreted proteins (stem cell factor (SCF) and CCL5) induced by ErbB2 expression that were dependent upon endogenous c-Jun expression. SCF and CCL5 were identified as transcriptionally induced by c-Jun. CCL5 rescued the c-Jun-deficient breast tumor cellular invasion phenotype. SCF rescued the c-Jun-deficient mammosphere production. Endogenous c-Jun thus contributes to ErbB2-induced mammary tumor cell invasion and self-renewal.

PMID:
20053993
PMCID:
PMC2832973
DOI:
10.1074/jbc.M110.100792
[Indexed for MEDLINE]
Free PMC Article
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