Effect of hypoxia on ALDH1A1 expression in MCF-7 human breast cancer cells and its correlation with Oct-4 pluripotency gene expression

Abstract

High aldehyde dehydrogenase (ALDH) activity is a marker of breast cancer stem cells (BCSCs). Our previous studies have indicated that, under hypoxia, stemness markers, such as Oct-4, could be modulated according to the ALDH1A1 expression in BCSC ALDH+ cells, thereby increasing their pluripotency. This study aimed to analyze the correlation between ALDH1A1 expression and Oct-4 pluripotency gene expression in MCF-7 human breast cancer cells under hypoxia in comparison with that in BCSC ALDH+ cells. This study determined the mRNA levels of ALDH1A1, Oct-4, and HIF-1α in MCF-7 breast cancer cells under hypoxia using one-step qRT-PCR, followed by normalization using 18S rRNA. Oct-4 expression was also analyzed via its correlation with ALDH1A1 expression. ALDH1A1 was expressed at a significantly higher level in 6-h hypoxic cells than in the corresponding normoxic cells, albeit the expression level started declining with the incubation time. Oct-4 and HIF-1α mRNA were also expressed at significantly higher levels in 6- and 24-h hypoxic cells, followed by decline in a time-dependent manner. The expression level pattern of these three genes peaked at 6 h under hypoxia, followed by a progressive decline, thereby confirming that the cells went into a hypoxic state. Hypoxia may alter the stemness properties of MCF-7 cells by increasing ALDH1A1 expression along with Oct-4 pluripotency gene expression. This study can contribute to further research on the implications of ALDH1A1 and hypoxia in breast cancer therapy.