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
Related in: MedlinePlus
Mentions: Finally, we examined whether knockdown of CD24 might increase the sensitivity of breast cancer cells to HER2-targeted therapy. Treatment of CD24-depleted or control BT-474 cells with lapatinib, a dual tyrosine kinase inhibitor for both the epidermal growth factor receptor and HER2, revealed that knockdown of CD24, indeed, enhanced the antiproliferative and death-promoting effects of lapatinib (Fig. 7a). We also found that HER2-90 cells are resistant to lapatinib (Fig. 7b), but that knockdown of CD24 increased the sensitivity of these cells to the antiproliferative and death-promoting effects of this agent (Fig. 7c). These data thus suggested that the expression of CD24 supports HER2-dependent cancer cell survival.
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.