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

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.
Authors	Xuanmao Jiao, Sanjay Katiyar, Nicole E Willmarth, Manran Liu, Xiaojing Ma, Neal Flomenberg, Michael P Lisanti, Richard G Pestell
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 11 Pg. 8218-26 (Mar 12 2010) ISSN: 1083-351X [Electronic] United States
PMID	20053993 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	CCL5 protein, human Chemokine CCL5 MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins c-jun Stem Cell Factor ERBB2 protein, human Receptor, ErbB-2
Topics	Animals Breast Neoplasms (genetics, pathology, physiopathology) Cell Division (physiology) Cell Line, Tumor Cell Movement (physiology) Chemokine CCL5 (metabolism) Epithelial Cells (pathology, physiology) Female Gene Expression Regulation, Neoplastic Humans Mice Mice, Transgenic Neoplasm Invasiveness (pathology, physiopathology) Phenotype Proto-Oncogene Mas Proto-Oncogene Proteins c-jun (genetics, metabolism) Receptor, ErbB-2 (genetics, metabolism) Stem Cell Factor (metabolism)

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