The association of HIF-2α expression with stemness and survival genes in human breast cancer stem cells (CD24-/CD44+) exposed to hypoxia

作者: L T Sen , J Septyani , J Halim , B Santoso , M B Ramadhan

DOI: 10.1088/1742-6596/1073/3/032066

关键词: Cancer stem cellHypoxia (medical)Stem cellSurvivinApoptosisViability assayKLF4CD44BiologyCancer research

摘要: Similar to normal stem cells, breast cancer cells (BCSCs) exist in prolonged hypoxia vivo and are cultured normoxic conditions (20% O2) vitro. Our previous study showed that the treatment of vitro BCSCs with 1% O2 upregulates HIF-1α. This aimed investigate HIF-2α expression under effects on its downstream gene (Oct-4, ALDH1, KLF4, c-MYC) along an associated survival gene, survivin. Human (CD24−/CD44+) were exposed (1% O2, 5% CO2) at intervals 0.5 h, 4 6 24 h. HIF2α, Oct-4, ALDH-1, c-MYC, survivin mRNA levels relatively quantified using qRT-PCR. Data analyzed Livak's formula one-way ANOVA. In contrast HIF-1α levels, gradually downregulated h treatment. concert, c-MYC as a measure stemness, significantly decreased following from The reduced these transcription factors suggests diminished proliferation possibility differentiation thus sensitizing them cell death. support this, downregulation was also shown throughout 0.5–24 hypoxia, which confirms our result demonstrated enhanced apoptosis. Hypoxia BCSCs, unlike resulted HIF-2 indicating acute may lead decreases stemness viability.

参考文章(27)
Nobuaki Kikyo, Steven Kellner, Transcriptional regulation of the Oct4 gene, a master gene for pluripotency Histology and Histopathology. ,vol. 25, pp. 405- 412 ,(2010) , 10.14670/HH-25.405
T Yu, X Chen, W Zhang, J Liu, R Avdiushko, D L Napier, A X Liu, J M Neltner, C Wang, D Cohen, C Liu, KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer Cell Death & Differentiation. ,vol. 23, pp. 207- 215 ,(2016) , 10.1038/CDD.2015.85
Mauricio Rodriguez-Torres, Alison L. Allan, Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors Clinical & Experimental Metastasis. ,vol. 33, pp. 97- 113 ,(2016) , 10.1007/S10585-015-9755-9
Brian Keith, M. Celeste Simon, Hypoxia-inducible factors, stem cells, and cancer. Cell. ,vol. 129, pp. 465- 472 ,(2007) , 10.1016/J.CELL.2007.04.019
Zheng Wang, Efrat Oron, Brynna Nelson, Spiro Razis, Natalia Ivanova, Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells Cell Stem Cell. ,vol. 10, pp. 440- 454 ,(2012) , 10.1016/J.STEM.2012.02.016
Anfei Liu, Xiya Yu, Shanrong Liu, Pluripotency transcription factors and cancer stem cells: small genes make a big difference. Chinese Journal of Cancer. ,vol. 32, pp. 483- 487 ,(2013) , 10.5732/CJC.012.10282
E B Rankin, A J Giaccia, The role of hypoxia-inducible factors in tumorigenesis. Cell Death & Differentiation. ,vol. 15, pp. 678- 685 ,(2008) , 10.1038/CDD.2008.21
Emmett V Schmidt, The role of c-myc in cellular growth control. Oncogene. ,vol. 18, pp. 2988- 2996 ,(1999) , 10.1038/SJ.ONC.1202751