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

Titlec-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion.
Publication TypeJournal Article
Year of Publication2010
AuthorsJiao X, Katiyar S, Willmarth NE, Liu M, Ma X, Flomenberg N, Lisanti MP, Pestell RG
JournalJ Biol Chem
Volume285
Issue11
Pagination8218-26
Date Published2010 Mar 12
ISSN1083-351X
KeywordsAnimals, Breast Neoplasms, Cell Division, Cell Line, Tumor, Cell Movement, Chemokine CCL5, Epithelial Cells, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Transgenic, Neoplasm Invasiveness, Phenotype, Proto-Oncogene Proteins c-jun, Receptor, erbB-2, Stem Cell Factor
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.

DOI10.1074/jbc.M110.100792
Alternate JournalJ Biol Chem
PubMed ID20053993
PubMed Central IDPMC2832973
Grant ListR01 CA075503 / CA / NCI NIH HHS / United States
R01 CA100223 / CA / NCI NIH HHS / United States
R01 CA120876 / CA / NCI NIH HHS / United States
R01CA75503 / CA / NCI NIH HHS / United States
R01CA120876 / CA / NCI NIH HHS / United States
R01 CA070896 / CA / NCI NIH HHS / United States
R01CA107382 / CA / NCI NIH HHS / United States
R01CA70896 / CA / NCI NIH HHS / United States
R01 CA107382 / CA / NCI NIH HHS / United States
P30 CA056036 / CA / NCI NIH HHS / United States

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