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Radiation promotes malignant phenotypes through SRC in breast cancer cells.

Kim RK, Cui YH, Yoo KC, Kim IG, Lee M, Choi YH, Suh Y, Lee SJ - Cancer Sci. (2014)

Bottom Line: However, the molecular mechanisms underlying radiation-induced cancer progression remain obscure.Importantly, radiation-activated SRC induced SLUG expression and caused epithelial-mesenchymal cell transition through phosphatidylinositol 3-kinase/protein kinase B and p38 MAPK signaling.In addition, downregulation of SRC also abolished radiation-acquired resistance of breast cancer cells to anticancer agents such as cisplatin, etoposide, paclitaxel, and IR.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.

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Irradiation promotes breast cancer stem cell populations through SRC signaling. (a) Quantification of CD44+/CD24− cell population by FACS analysis in MCF7 and SKBR3 cancer cells after irradiation. (b) Quantification of CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting SRC (si-SRC) or scrambled control siRNA (si-Con) prior to irradiation. (c, d) Western blot analysis for CD44, SOX2, Notch-1, and Notch-2 (c), and immunocytochemistry for CD44 (d) in MCF7 cancer cells transfected with siRNA targeting SRC or scrambled control siRNA prior to irradiation. (e, f) Quantification of the CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting AKT (si-AKT) (e) or p38 MAPK (si-p38) (f) prior to irradiation. (g, h) Quantification of the CD44+ cell population by FACS analysis in MCF7 (g) and SKBR3 (h) cancer cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. (i) Western blot analysis for SOX2 in MCF7 cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. β-actin was used as a loading control. Error bars represent mean ± SD of triplicate samples. *P < 0.05; **P < 0.01. Cont, control.
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fig04: Irradiation promotes breast cancer stem cell populations through SRC signaling. (a) Quantification of CD44+/CD24− cell population by FACS analysis in MCF7 and SKBR3 cancer cells after irradiation. (b) Quantification of CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting SRC (si-SRC) or scrambled control siRNA (si-Con) prior to irradiation. (c, d) Western blot analysis for CD44, SOX2, Notch-1, and Notch-2 (c), and immunocytochemistry for CD44 (d) in MCF7 cancer cells transfected with siRNA targeting SRC or scrambled control siRNA prior to irradiation. (e, f) Quantification of the CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting AKT (si-AKT) (e) or p38 MAPK (si-p38) (f) prior to irradiation. (g, h) Quantification of the CD44+ cell population by FACS analysis in MCF7 (g) and SKBR3 (h) cancer cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. (i) Western blot analysis for SOX2 in MCF7 cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. β-actin was used as a loading control. Error bars represent mean ± SD of triplicate samples. *P < 0.05; **P < 0.01. Cont, control.

Mentions: As EMT is often associated with the CSC population, we examined whether radiation-activated SRC is also involved in expansion of the CSC population. To this end, we analyzed the CD44+/CD24− cell population in both MCF7 and SKBR3 breast cancer cells after exposure to a single dose (6 Gy) or fractionated dose (2 Gy ×3) of radiation. Notably, irradiation caused an increase in the CD44+/CD24− cell population, well-known as CSCs in breast cancer (Fig.4a). Intriguingly, fractionated irradiation had more effect on the increase of CD44+/CD24− cells compared to single irradiation, although irradiated doses were equal. However, treatment with siRNA targeting SRC suppressed the radiation-induced expansion of CD44+ cells to basal levels (Fig.4b).


Radiation promotes malignant phenotypes through SRC in breast cancer cells.

Kim RK, Cui YH, Yoo KC, Kim IG, Lee M, Choi YH, Suh Y, Lee SJ - Cancer Sci. (2014)

Irradiation promotes breast cancer stem cell populations through SRC signaling. (a) Quantification of CD44+/CD24− cell population by FACS analysis in MCF7 and SKBR3 cancer cells after irradiation. (b) Quantification of CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting SRC (si-SRC) or scrambled control siRNA (si-Con) prior to irradiation. (c, d) Western blot analysis for CD44, SOX2, Notch-1, and Notch-2 (c), and immunocytochemistry for CD44 (d) in MCF7 cancer cells transfected with siRNA targeting SRC or scrambled control siRNA prior to irradiation. (e, f) Quantification of the CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting AKT (si-AKT) (e) or p38 MAPK (si-p38) (f) prior to irradiation. (g, h) Quantification of the CD44+ cell population by FACS analysis in MCF7 (g) and SKBR3 (h) cancer cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. (i) Western blot analysis for SOX2 in MCF7 cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. β-actin was used as a loading control. Error bars represent mean ± SD of triplicate samples. *P < 0.05; **P < 0.01. Cont, control.
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fig04: Irradiation promotes breast cancer stem cell populations through SRC signaling. (a) Quantification of CD44+/CD24− cell population by FACS analysis in MCF7 and SKBR3 cancer cells after irradiation. (b) Quantification of CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting SRC (si-SRC) or scrambled control siRNA (si-Con) prior to irradiation. (c, d) Western blot analysis for CD44, SOX2, Notch-1, and Notch-2 (c), and immunocytochemistry for CD44 (d) in MCF7 cancer cells transfected with siRNA targeting SRC or scrambled control siRNA prior to irradiation. (e, f) Quantification of the CD44+ cell population by FACS analysis in MCF7 cancer cells transfected with siRNA targeting AKT (si-AKT) (e) or p38 MAPK (si-p38) (f) prior to irradiation. (g, h) Quantification of the CD44+ cell population by FACS analysis in MCF7 (g) and SKBR3 (h) cancer cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. (i) Western blot analysis for SOX2 in MCF7 cells 48 h after transfection with SRC WT, mutant form SRC Y527F, or control vector pcDNA3.1. β-actin was used as a loading control. Error bars represent mean ± SD of triplicate samples. *P < 0.05; **P < 0.01. Cont, control.
Mentions: As EMT is often associated with the CSC population, we examined whether radiation-activated SRC is also involved in expansion of the CSC population. To this end, we analyzed the CD44+/CD24− cell population in both MCF7 and SKBR3 breast cancer cells after exposure to a single dose (6 Gy) or fractionated dose (2 Gy ×3) of radiation. Notably, irradiation caused an increase in the CD44+/CD24− cell population, well-known as CSCs in breast cancer (Fig.4a). Intriguingly, fractionated irradiation had more effect on the increase of CD44+/CD24− cells compared to single irradiation, although irradiated doses were equal. However, treatment with siRNA targeting SRC suppressed the radiation-induced expansion of CD44+ cells to basal levels (Fig.4b).

Bottom Line: However, the molecular mechanisms underlying radiation-induced cancer progression remain obscure.Importantly, radiation-activated SRC induced SLUG expression and caused epithelial-mesenchymal cell transition through phosphatidylinositol 3-kinase/protein kinase B and p38 MAPK signaling.In addition, downregulation of SRC also abolished radiation-acquired resistance of breast cancer cells to anticancer agents such as cisplatin, etoposide, paclitaxel, and IR.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.

Show MeSH
Related in: MedlinePlus