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

• Published in: Molecular and cellular biochemistry Vol. 400; no. 1-2; pp. 41 - 50
• Main Authors: Oliveira, Bruno Rodrigues, Figueiredo, Marcio Azevedo, Trindade, Gilma Santos, Marins, Luis Fernando
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2015; Springer; Springer Nature B.V
• Subjects: Amino acids; Biochemistry; Biomedical and Life Sciences; Cancer; Cardiology; Cell Line, Tumor; Chemotherapy; Drug resistance; Drug Resistance, Multiple - genetics; Gene expression; Genotype & phenotype; Humans; Leukemia; Leukemia, Erythroblastic, Acute - drug therapy; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - pathology; Life Sciences; Medical Biochemistry; Mutation; Neoplastic Stem Cells - pathology; Octamer Transcription Factor-3 - genetics; Oncology; Phosphorylation; Stem cells; Transcription factors; Phosphorylation motifs; Transcription factors; ABC transporters; K562-Lucena; K562; Gene expression
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-014-2260-7

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.