Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells.
Bottom Line: However, resistance to HER2-targeted therapy remains a major clinical problem.HER2-positive breast tumors are predominantly positive for CD24, suggesting that the expression of the two molecules is related.Flow cytometry thus revealed that the percentage of CD24-positive cells was markedly higher in the HER2-positive fraction than in the HER2-negative fraction.
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: To determine if HER2 overexpression might affect CSC properties, we examined sphere formations of HER2-90 and 231-Luc cells. The numbers of spheres formed with a diameter of >100 μm were counted. HER2-90 cells formed significantly fewer spheres than did 231-Luc cells (Fig. 2a,b). Cells were also cultured using 1% methylcellulose containing a medium to avoid cell aggregation. In contrast to 231-Luc cells, HER2-90 cells did not form sphere-like colonies in the presence of methylcellulose (Fig. 2a,b). An examination of ALDH1 activity, a functional marker for breast cancer CSC,(17) revealed that overexpression of HER2 decreased the proportion of ALDEFLUOR-positive CSC (Fig. 2c). To determine the ability of 231-Luc and HER2-90 cells to initiate tumors, we injected cells into a mammary fat pad of female NOD/SCID mice, which revealed that there was no difference in the frequency of tumor initiation (Fig. 2d). These results suggested that overexpression of HER2 decreased representative CSC properties, such as the sphere-forming ability and ALDH1 activity, and did not affect the tumorigenicity of 231-Luc triple-negative breast cancer cells.
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.