Title | c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Jiao X, Katiyar S, Willmarth NE, Liu M, Ma X, Flomenberg N, Lisanti MP, Pestell RG |
Journal | J Biol Chem |
Volume | 285 |
Issue | 11 |
Pagination | 8218-26 |
Date Published | 2010 Mar 12 |
ISSN | 1083-351X |
Keywords | Animals, 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. |
DOI | 10.1074/jbc.M110.100792 |
Alternate Journal | J Biol Chem |
PubMed ID | 20053993 |
PubMed Central ID | PMC2832973 |
Grant List | R01 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 |
Submitted by mam2155 on March 24, 2014 - 4:16pm