Oct4 suppresses IR‑induced premature senescence in breast cancer cells through STAT3- and NF‑κB-mediated IL‑24 production

International Journal of Oncology
Jeong-Yub KimMyung-Jin Park

Abstract

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells that have been proposed to be a primary cause of failure of therapies, including ionizing radiation (IR). Their embryonic stem-like signature is associated with poor clinical outcome. In the present study, the function of octamer-binding transcription factor 4 (Oct4), an embryonic stem cell factor, in the resistance of BCSCs to IR was investigated. Mammosphere cells exhibited increased expression of stemness-associated genes, including Oct4 and sex‑determining region Y‑box 2 (Sox2), and were more resistant to IR compared with serum-cultured monolayer cells. IR‑resistant MCF7 cells also exhibited significantly increased expression of Oct4. To investigate the possible involvement of Oct4 in IR resistance of breast cancer cells, cells were transfected with Oct4. Ectopic expression of Oct4 increased the clonogenic survival of MCF7 cells following IR, which was reversed by treatment with small interfering RNA (siRNA) targeting Oct4. Oct4 expression decreased phosphorylated histone H2AX (γ-H2AX) focus formation and suppressed IR‑induced premature senescence in these cells. Mammosphere, IR‑resistant and Oct4‑overexpressing MCF7 cells exhibited enhanced p...Continue Reading

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Citations

Jan 14, 2020·Molecular Oncology·Carmen Griñán-LisónJuan Antonio Marchal
Jul 15, 2020·Cells·Christine E HellwegAgapios Sachinidis

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Methods Mentioned

BETA
PCR
transfection
FACS

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