已知干扰素诱导的跨膜蛋白 1 (IFITM1) 参与乳腺癌进展。我们的目的是研究其在雌激素受体（ER）阳性乳腺癌细胞（具有野生型p53）和他莫昔芬耐药乳腺癌细胞中的作用。ER阳性乳腺癌细胞系，具有野生型p53的MCF-7和具有野生型p53的T47D使用突变体p53。我们通过用 4-羟基他莫昔芬长期培养 MCF-7 细胞，建立了 MCF-7 衍生的他莫昔芬耐药细胞系 (TamR)。MCF-7 细胞中的 IFITM1 抑制显着降低了细胞生长和迁移。与对照 MCF-7 细胞相比，使用 siRNA 或鲁索替尼抑制 IFITM1 的 MCF-7 细胞在他莫昔芬处理后显示细胞活力降低。出乎意料的是，与 MCF-7 细胞相比，TamR 细胞中 IFITM1 的 mRNA 和蛋白水平降低。使用 siRNA 或鲁索替尼抑制 IFITM1 的 TamR 细胞在用他莫昔芬处理后显示细胞活力没有变化。使用 siRNA 敲低 P53 降低了 MCF-7 细胞中 IRF9 的 mRNA 水平，增加了 SOCS3 的 mRNA 和蛋白水平，表明 p53 的丢失或突变可以通过乳腺癌中的 JAK/STAT 信号通路影响 IFITM1 的诱导。此外，使用 siRNA 敲低 p53 的 MCF-7 细胞在他莫昔芬治疗或 IFITM1 抑制后显示细胞活力没有下降，表明 p53 状态可能对他莫昔芬治疗或 IFITM1 抑制后细胞死亡很重要。IFITM1 抑制可能增强对他莫昔芬的敏感性关于野生型 p53、ER 阳性乳腺癌细胞中 p53 依赖性 IFN 信号增强的研究。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

Interferon-induced trans-membrane protein 1 (IFITM1) is known to be involved in breast cancer progression. We aimed to investigate its role in estrogen receptor (ER)-positive breast cancer cells with wild-type p53 and tamoxifen-resistant breast cancer cells.The ER-positive breast cancer cell lines, MCF-7 with wild-type p53 and T47D with mutant p53, were used. We established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen.IFITM1 inhibition in MCF-7 cells significantly decreased cell growth and migration. MCF-7 cells with suppression of IFITM1 using siRNA or ruxolitinib showed reduced cell viability after tamoxifen treatment compared with that in the control MCF-7 cells. Unexpectedly, mRNA and protein levels of IFITM1 were decreased in TamR cells compared with those in MCF-7 cells. TamR cells with suppression of IFITM1 using siRNA or ruxolitinib showed no change in cell viability after treatment with tamoxifen. P53 knockdown using siRNA reduced the mRNA levels of IRF9 and increased mRNA and protein levels of SOCS3 in MCF-7 cells, suggesting that loss or mutation of p53 can affect the induction of IFITM1 via the JAK/STAT signaling pathway in breast cancer. Furthermore, MCF-7 cells with p53 knockdown using siRNA showed no decrease in cell viability after tamoxifen treatment or IFITM1 inhibition, indicating that p53 status may be important for cell death after tamoxifen treatment or IFITM1 inhibition.IFITM1 inhibition may enhance the sensitivity to tamoxifen based on p53-dependent enhancement of IFN signaling in wild-type p53, ER-positive breast cancer cells.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.