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OCT4 mutations in human erythroleukemic cells: implications for multiple drug resistance (MDR) phenotype

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Abstract

The OCT4 transcription factor is a crucial stem cells marker and it has been related to the cancer stem cells concept. Moreover, it has also been associated to the multiple drug resistance (MDR) phenotype. Our first results pointed out a straight relation between OCT4 and ABC transporters in K562-derivative MDR (Lucena) cells. Sequencing of ABC promoters did not reveal any mutation that could explain the differential expression of OCT4 in Lucena cells. Furthermore, sequencing of the homeobox domain region from the OCT4 gene isolated from both cell lines evinced, for the first time, that this transcription factor is a target of mutations and might be related to the MDR phenotype. The encountered mutations implied in several amino acids substitutions in both cell lines. K562 had seven amino acids substituted (three of them exclusive), while Lucena had 13 substitutions (nine of them exclusive). In addition, an in silico search for phosphorylation motifs within the amino acid stretch compared showed that human normal OCT4 has seven potential phosphorylation motifs. However, K562 has lost one phosphorylation motif and Lucena two of them. These findings bring OCT4 as an important target for cancer treatment, especially those resistant to chemotherapy.

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Acknowledgments

We thank the Instituto de Bioquímica Médica Leopoldo de Meis from the Universidade Federal do Rio de Janeiro (UFRJ) for providing the cell lines used in this study. Also, we thank CAPES (coordenação de aperfeiçoamento de pessoal de nível superior) for scholarship to B. Oliveira. L. F. Marins is a research fellow from CNPq (Proc. No. 304675/2011-3).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Instituto de Ciências Biológicas (ICB), Universidade Federal do Rio Grande - FURG, Rio Grande. Av. Italia Km8, Rio Grande, RS, 96203-900, Brazil

    Bruno Rodrigues Oliveira, Marcio Azevedo Figueiredo, Gilma Santos Trindade & Luis Fernando Marins

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  1. Bruno Rodrigues Oliveira
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  2. Marcio Azevedo Figueiredo
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  3. Gilma Santos Trindade
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  4. Luis Fernando Marins
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Correspondence to Luis Fernando Marins.

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Oliveira, B.R., Figueiredo, M.A., Trindade, G.S. et al. OCT4 mutations in human erythroleukemic cells: implications for multiple drug resistance (MDR) phenotype. Mol Cell Biochem 400, 41–50 (2015). https://doi.org/10.1007/s11010-014-2260-7

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  • DOI: https://doi.org/10.1007/s11010-014-2260-7

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