Bcl-3 promotes proliferation and chemosensitivity in BL1 subtype of TNBC cells
Bcl-3 promotes proliferation and chemosensitivity in BL1 subtype of TNBC cells
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Bcl-3促进TNBC细胞BL1亚型的增殖和化疗敏感性
DOI：
10.1093/abbs/gmy117
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发表时间：
2018-11-01
影响因子：
3.7
通讯作者：
Zhang, Xiaoren
中科院分区：
文献类型：
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作者：
Huo, Junhaohui;Chen, Xi;Zhang, Xiaoren
Bcl-3 是多种恶性肿瘤中已确定的癌基因。在这项研究中，我们研究了 Bcl-3 在 BL1 亚型三阴性乳腺癌 (TNBC) 中的双重作用。 BL1亚型TNBC的特点是细胞周期基因表达增加，并且在所有亚型中对化疗的敏感性最高。 Bcl-3 与 BL1 患者更好的预后相关。 BL1 细胞 MDA-MB-468 中的 Bcl-3 敲低通过促进 p27 并减少 mRNA 和蛋白质水平上的 c-Myc 和 skp2 表达来诱导细胞增殖抑制和 G1/S 转变停滞。同时，Bcl-3增强MDA-MB-468对化疗药物ABX和PTX的敏感性。此外，该调节机制仅限于 BL1 细胞，在 TNBC 细胞的典型 MSL 亚型 SUM159PT 中不发生。这些数据表明，Bcl-3可能是BL1亚型TNBC患者诊断、治疗和预后的潜在临床生物标志物。
Bcl-3 is an established oncogene in diverse malignant tumors. In this study, we investigated a dual role of Bcl-3 in BL1-subtype triple-negative breast cancer (TNBC). The BL1-subtype TNBC is featured by increasing cell cycle gene expression and the highest sensitivity to chemotherapy among all subtypes. Bcl-3 is associated with a better prognosis in BL1 patients. Bcl-3 knockdown in BL1 cell MDA-MB-468 induces the inhibition of cell proliferation and the G1/S transition arrest by promoting p27 and reducing the expressions of c-Myc and skp2 at mRNA and protein levels. Meanwhile, Bcl-3 enhances the sensitivity of MDA-MB-468 to chemotherapeutics ABX and PTX. Furthermore, the regulation mechanisms are restricted to BL1 cell and do not occur in SUM159PT, a typical MSL subtype of TNBC cell. These data suggest that Bcl-3 may be a potential clinical biomarker for diagnosis, treatment, and prognosis of patients with BL1-subtype TNBC.