Expression Profiling of HMGB1 Suppressed MCF‐7 Cells

Abstract

The high mobility group protein HMGB1 is the most abundant non-histone chromosomal protein in higher eukaryotes and it has long been known as an architectural transcription factor involved in gene activation as well as in other nuclear processes. More recently, HMGB1 has been found to have extra-cellular functions as a late mediator in immune response and also as a cytokine. We have been interested in how the human HMGB1 gene is regulated as well as how HMGB1 regulates other genes in the cell. Using an anti-sense strategy, we have established an MCF-7 breast cancer cell line that expresses HMGB1 at only half the level of the original cell line. cDNA microarrays of the expression profile of these two cell lines were compared and genes with significant differential expression levels in these two cell lines were identified. Two of the genes expression of which were found to have significantly lowered with the decrease in HMGB1 expression are TP53 and MDM2, indicating the importance of HMGB1 in TP53 expression and cell cycle checkpoint control. In addition, expression of the acid alpha-glucosidase (GAA) gene has also been found to have lowered with the decrease in HMGB1 expression. GAA is an enzyme involved in the glycogen metabolism pathway and our finding further shows that HMGB1 is also important in glycogen/glucose metabolism.