79923

NANOG

-;Nanog homeobox;NANOG;Nanog homeobox

hNanog|homeobox protein NANOG|homeobox transcription factor Nanog|homeobox transcription factor Nanog-delta 48

12p13.31

protein-coding

OBJECTIVES: Atypical teratoid/rhabdoid tumor (AT/RT) and medulloblastoma (MB) are the most malignant primary brain tumors in early childhood. AT/RT is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. The biological features and clinical outcomes of AT/RT and MB are extremely different. In this study, we used microarray as a platform to distinguish these two tumors with thedefinitive diagnostic marker as well as the profiling of expression genes. METHODS: In order to clarify the pathogenesis and find the biological markers for AT/RT, we established a derivative AT/RT primary cell culture. The differential profiling between AT/RT and MB were analyzed by using microarray method. RESULTS: With the use of the microarray method, we demonstrated that 15 genes were significantly changed (at least 5-fold in upregulation and 1/5-fold in downregulation) between AT/RT and MB in tissues and cell lines. The quantitativereverse transcription-polymerase chain reaction analyses further confirmed that mRNA expression levels of SERPINI1 and osteopontin were highly expressed in AT/RT cells and tissues than those in MB. Importantly, our microarray result suggestedthat AT/RT presents the stemness-like pattern and expression profiling of embryonic stem cells as well as high mRNA expressions of Oct-4, Nanog, Sox-2, and c-Myc. CONCLUSIONS: Our study demonstrated the differential gene expression profiling between AT/RT and MB. Based on the microarray findings, AT/RTs presentembryonic stem-like gene recapitulation and further provide novel insights into their underlying biology.

cancer stem-like cells have been identified in both primary tumors and in cell lines and seem to have a high degree of inherent resistance to traditional chemotherapeutic agents. Relapsed cancers including neuroblastoma are generally chemotherapy-resistant and carry a very poor prognosis. We investigated the sidepopulations of three pairs of neuroblastoma cell lines derived from single patients at the time of their initial presentation and then at relapse after multimodality therapy. We found that the size of the side populations in the relapsed cell lines was significantly increased compared with its paired pretreatment cell line. In addition, these side population cells showed increased proliferation and were significantly more efficient at forming colonies in soft agar than their prerelapse pair. Gene expression analysis of the stem cell genesNANOG and POU5F1 (Oct3/4) showed increased expression in the unsorted relapsed cell lines compared with pretreatment lines as well as in the side populations of the relapsed versus prerelapse cell line pairs. The increased size, proliferative ability, and colony-forming efficiency of the side populations of the postrelapse cell lines demonstrated in this study suggest that a population of stemlike cells is not being efficiently targeted by conventional therapy and implies that strategies to specifically target the stem cell fraction of neuroblastomas are needed to improve outcomes in this devastating childhood disease.

OBJECTIVES: A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to bedefined. METHODS: Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (>100 mum in diameter) counting, respectively. RESULTS: Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu(2+)-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effectiveagainst spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells. CONCLUSIONS: The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.