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1.
Oncogene ; 36(13): 1862-1872, 2017 03 30.
Article in English | MEDLINE | ID: mdl-27721402

ABSTRACT

Whereas accumulating studies have supported the cancer stem cell theory, a specific therapy targeting a cancer stem cell subpopulation has not been established. Here, we show that dual-specificity tyrosine phosphorylation-kinase 2 (DYRK2) is a novel negative regulator for formation of breast cancer stem cells. Downregulation of DYRK2 promotes cancer stem-like traits in vitro, tumourigenesis in vivo and the proportion of the cancer stem cell population in human breast cancer tissues. We found that Krupple-like factor 4 (KLF4) serves as a key mediator of DYRK2's control over the cancer stem phenotype. Reduced DYRK2 expression increases KLF4 expression, which induces cancer stem-like properties. We identified androgen receptor (AR) as a transcription factor binding to the KLF4 promoter region; this process is dependent on DYRK2 kinase activity. Our findings delineate a mechanism of cancer stem cell regulation by the DYRK2-AR-KLF4 axis in breast cancer. Targeting of this pathway may be a promising strategy against breast cancer stem cells.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors/genetics , Neoplastic Stem Cells/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Female , Humans , Kruppel-Like Factor 4 , Models, Biological , Phenotype , Phosphorylation , Receptors, Androgen/metabolism , Transcriptional Activation , Dyrk Kinases
2.
Jpn Circ J ; 48(12): 1406-10, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6512950

ABSTRACT

Frank vectorcardiograms recorded on magnetic tape were analyzed by a computer. The study population was 835 normal children aged from 6 to 16. Magnitudes, angles (azimuth, elevation) of the maximal spatial QRS vector and QRS duration were calculated. The magnitude of maximal spatial QRS vector increased significantly in males compared to those in females at ages 9-10, 11-12 (p less than 0.01) and 15-16 (p less than 0.001). Though there was no significant difference of elevation in either sex, azimuth tended to move more anteriorly in females than in males. QRS duration in males became longer with increasing age, while in females at age 15-16, it decreased (p less than 0.001).


Subject(s)
Computers , Vectorcardiography , Adolescent , Age Factors , Child , Female , Humans , Male , Sex Factors
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