title: The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis.
abstract: Nanog is a transcription factor required for maintaining the pluripotency of embryonic stem cells, and is not expressed in most normal adult tissues. However, recent studies have indicated that Nanog is overexpressed in many types of human cancers, including breast cancer. To elucidate the physiological roles of Nanog in tumorigenesis, we developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Our findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. In this context, Nanog promotes the migration and invasion of breast cancer cells. Microarray analysis has shown that the ectopic expression of Nanog deregulates the expression of numerous genes associated with tumorigenesis and metastasis, such as the PDGFRα gene. Our findings demonstrate the involvement of Nanog in breast cancer metastasis, and provide the basis for the reported correlation between Nanog expression and poor prognosis of human breast cancer patients. As Nanog is not expressed in most adult tissues, these findings identify Nanog as a potential therapeutic target in the treatment of Nanog-expressing metastatic breast cancer.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Mazur
authors.affiliation: Center for Regenerative Medicine and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Appella
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse