Prognostic significance of NANOG and KLF4 for breast cancer.
ABSTRACT BACKGROUND: Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients. METHODS: In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis. RESULTS: Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014). CONCLUSIONS: Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.
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ABSTRACT: Kruppel-like factor 4 (KLF4) is a transcription factor that participates in both tumor suppression and oncogenesis. To determine the association of KLF4 with tumorigenesis, we integrated data assembled in the Oncomine database and discovered a decrease in KLF4 gene transcripts in breast cancers. Further analysis of the database also showed a correlation between KLF4 expression and estrogen receptor-alpha (ERalpha) positivity. Knockdown of KLF4 in MCF-7 cells elevated the growth rate of these cells in the presence of estrogen. Therefore, we examined the interaction between KLF4 and ERalpha, and found that KLF4 bound to the DNA-binding region of ERalpha. KLF4 thus inhibits the binding of ERalpha to estrogen response elements in promoter regions, resulting in a reduction in ERalpha target gene transcription. Earlier studies have reported that KLF4 is transcriptionally activated by p53 following DNA damage. We also showed that activation of p53 decreased the transcriptional activity of ERalpha by elevating KLF4 expression. Our studies discovered a novel molecular network between p53, KLF4 and ERalpha. As both p53 and ERalpha are involved in cell growth and apoptosis, these results may explain why KLF4 possesses both tumor suppressive and oncogenic functions in breast cancers.Oncogene 07/2009; 28(32):2894-902. · 7.36 Impact Factor
- Acta Biochimica Et Biophysica Sinica - ACTA BIOCHIM BIOPHYS SINICA. 01/2008; 40(7):554-564.
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ABSTRACT: Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.Science 01/2008; 318(5858):1917-20. · 31.20 Impact Factor