Figure 6 from MUC1-C Dictates PBRM1-Mediated Chronic Induction of Interferon Signaling, DNA Damage Resistance, and Immunosuppression in Triple-Negative Breast Cancer
Year: 2025
Type: other
Abstract: Targeting MUC1-C in TNBC CSCs inhibits self-renewal capacity and circumvents DNA damage resistance. A, BT-549/tet-MUC1shRNA cells were treated with vehicle or DOX for 7 days and then assayed for tumorsphere formation in the absence and presence of 0.2 μmol/L CBDCA for 7 days (A, top); scale bar, 100 μm. The results (mean ± SD of 3 biological replicates) are expressed as the number of mammospheres (A, lower). B, BT-549/tet-MUC1shRNA mammospheres treated with vehicle or DOX in the absence and presence of 2 μmol/L CBDCA for 2 days were assayed by ICC analysis for visualization of γH2AX foci; scale bar, 50 μm. C, BT-549 cells treated with vehicle or 0.75 μmol/L GO-203 in the absence and presence of 0.2 μmol/L CBDCA were assayed for mammosphere formation at 8 days (top); scale bar, 100 μm. The results (mean ± SD of 3 biological replicates) are expressed as the number of mammospheres (bottom).D, BT-549 mammospheres treated with vehicle or 2.5 μmol/L GO-203 in the absence and presence of 2 μmol/L CBDCA for 2 days were assayed by ICC analysis for visualization of γH2AX foci; scale bar, 50 μm. E, Lysates from parental MDA-MB-436 and olaparib-resistant MDA-MB-436RR cells were immunoblotted with antibodies against the indicated proteins. F, MDA-MB-436RR cells treated with 5 μmol/L GO-203 for 2 days were immunoblotted with antibodies against the indicated proteins. G, MDA-MB-436RR cells treated with vehicle or 5 μmol/L GO-203 were assayed for mammosphere formation at 7 days (left); scale bar, 100 μm. The results (mean±SD of 3 biological replicates) are expressed as the number of mammospheres (right). H, MDA-MB-436RR mammospheres treated with vehicle or 2.5 μmol/L GO-203 for 2 days were assayed by ICC analysis for visualization of γH2AX foci; scale bar, 50 μm. I, Six-week-old nude mice were injected subcutaneously in the flank with 3×106 MDA-MB-436RR cells. Mice pair-matched into two groups when tumors reached 100 to 150 mm3 were treated intraperitoneally daily with PBS or GO-203 for 26 days. Tumor volumes are expressed as the mean±SEM for 6 mice. J, Lysates from tumors exposed for 5 days to GO-203 were immunoblotted with antibodies against the indicated proteins. *, P ≤ 0.05; ***, P ≤ 0.001.
Authors: Nami Yamashita, Yoshihiro Morimoto, Atsushi Fushimi, Rehan Ahmad, Atrayee Bhattacharya, Tatsuaki Daimon, Naoki Haratake, Yuka Inoue, Satoshi Ishikawa, Masaaki Yamamoto, Tsuyoshi Hata, Sayuri Akiyoshi, Qiang Hu, Tao Liu, Henry Withers, Song Liu, Geoffrey I. Shapiro, Tomoharu Yoshizumi, Mark D. Long, Donald Kufe
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4416764800