Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells.
Bottom Line: We found that expression of CD24 was increased by stable overexpression of HER2.Knockdown of CD24 also suppressed the phosphorylation of Akt, which functions downstream of HER2 and PI3K to promote cell survival.Our results thus indicate that CD24 supports both the expression of HER2 and the consequent activation of PI3K-Akt signaling.
Affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan; Department of Breast Oncology, Tokyo Medical University, Tokyo, Japan.Show MeSH
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Mentions: We next examined the expression of HER2, CD24 and CD44 in five HER2-positive breast cancer cell lines: BT-474, HCC202, SKBR3, ZR-75-1 and HCC1569. Flow cytometry showed that the CD44+CD24− subpopulation constituted 2.65%, 0.057%, 0.143%, 1.42% and 91.7% of cells in these lines, respectively (Fig. 4a). Next, we measured CD24 expression levels in the top 20% fraction of HER2-high cells and the bottom 20% fraction of HER2-low/- cells of each cell line (Fig. 4b). For BT-474, which has an amplification of HER2 gene, the CD24-positive subpopulation was 97.1% in the HER2-high fraction but 73.4% in the HER2-low/- fraction. For ZR-75-1, which has a normal level of HER2, the proportion of CD24-positive cells was 97.2% in the HER2-high fraction but only 27.4% in the HER2-low/- fraction (Fig. 4c). A similar pattern was apparent for the other three HER2-amplified cell lines. The expression of CD24 was thus higher in HER2-high cells than in HER2-low/- cells for all five breast cancer cell lines.
Affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan; Department of Breast Oncology, Tokyo Medical University, Tokyo, Japan.