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Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells.

Hosonaga M, Arima Y, Sugihara E, Kohno N, Saya H - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

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.

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Knockdown of CD24 sensitizes human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells to lapatinib treatment. (a) BT-474 cells were transfected with control (GAPD) or CD24 siRNA for 24 h and then exposed to 0.5 μM lapatinib for 48 h for cell death assay or for the indicated times, after which cell viability was determined with an Cell titer Glo assay kit (top panel) and cell death was evaluated by staining with trypan blue (bottom panels). Cell proliferation data are expressed as fold change in relative luminescence units (RLU) relative to time 0, and all quantitative data are means ± SD from triplicate experiments. *P < 0.05, **P < 0.01 (Student's t-test). Scale bars, 100 μm. (b) HER2-90 cells were incubated with the indicated concentrations of lapatinib or with DMSO vehicle for the indicated times, after which cell viability was determined with an assay kit as in (a). (c) HER2-90 cells were transfected with control (GAPD) or CD24 siRNAs for 24 h and then treated with 15 μM lapatinib for 48 h, after which cell viability and cell death were determined as in (a).
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fig07: Knockdown of CD24 sensitizes human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells to lapatinib treatment. (a) BT-474 cells were transfected with control (GAPD) or CD24 siRNA for 24 h and then exposed to 0.5 μM lapatinib for 48 h for cell death assay or for the indicated times, after which cell viability was determined with an Cell titer Glo assay kit (top panel) and cell death was evaluated by staining with trypan blue (bottom panels). Cell proliferation data are expressed as fold change in relative luminescence units (RLU) relative to time 0, and all quantitative data are means ± SD from triplicate experiments. *P < 0.05, **P < 0.01 (Student's t-test). Scale bars, 100 μm. (b) HER2-90 cells were incubated with the indicated concentrations of lapatinib or with DMSO vehicle for the indicated times, after which cell viability was determined with an assay kit as in (a). (c) HER2-90 cells were transfected with control (GAPD) or CD24 siRNAs for 24 h and then treated with 15 μM lapatinib for 48 h, after which cell viability and cell death were determined as in (a).

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.


Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells.

Hosonaga M, Arima Y, Sugihara E, Kohno N, Saya H - Cancer Sci. (2014)

Knockdown of CD24 sensitizes human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells to lapatinib treatment. (a) BT-474 cells were transfected with control (GAPD) or CD24 siRNA for 24 h and then exposed to 0.5 μM lapatinib for 48 h for cell death assay or for the indicated times, after which cell viability was determined with an Cell titer Glo assay kit (top panel) and cell death was evaluated by staining with trypan blue (bottom panels). Cell proliferation data are expressed as fold change in relative luminescence units (RLU) relative to time 0, and all quantitative data are means ± SD from triplicate experiments. *P < 0.05, **P < 0.01 (Student's t-test). Scale bars, 100 μm. (b) HER2-90 cells were incubated with the indicated concentrations of lapatinib or with DMSO vehicle for the indicated times, after which cell viability was determined with an assay kit as in (a). (c) HER2-90 cells were transfected with control (GAPD) or CD24 siRNAs for 24 h and then treated with 15 μM lapatinib for 48 h, after which cell viability and cell death were determined as in (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4317915&req=5

fig07: Knockdown of CD24 sensitizes human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells to lapatinib treatment. (a) BT-474 cells were transfected with control (GAPD) or CD24 siRNA for 24 h and then exposed to 0.5 μM lapatinib for 48 h for cell death assay or for the indicated times, after which cell viability was determined with an Cell titer Glo assay kit (top panel) and cell death was evaluated by staining with trypan blue (bottom panels). Cell proliferation data are expressed as fold change in relative luminescence units (RLU) relative to time 0, and all quantitative data are means ± SD from triplicate experiments. *P < 0.05, **P < 0.01 (Student's t-test). Scale bars, 100 μm. (b) HER2-90 cells were incubated with the indicated concentrations of lapatinib or with DMSO vehicle for the indicated times, after which cell viability was determined with an assay kit as in (a). (c) HER2-90 cells were transfected with control (GAPD) or CD24 siRNAs for 24 h and then treated with 15 μM lapatinib for 48 h, after which cell viability and cell death were determined as in (a).
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.

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.

View Article: PubMed Central - PubMed

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