Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, USA.
Cancer Lett. 2012 Sep 28;322(2):119-26. doi: 10.1016/j.canlet.2012.02.033. Epub 2012 Mar 17.
Breast cancer (BC) is an aggressive and high mortality cancer that can be classified into five molecular subtypes, based on gene expression profiling. The extreme heterogeneity poses difficulties for understanding and treating BC. Among many risk factors, inflammation plays a causal role in BC progression and recurrence, wherein NFkB and glucocorticoid receptor (GR) are critical transcription factors in regulating inflammation. NFkB is generally pro-inflammatory, and GR is anti-inflammatory, constituting a Yin-Yang mode in regulation. Thus, the crosstalk between these two transcription factors exerts even more important functions in determining the survival or apoptosis of BC cells. NFkB is widely involved in the initiation and progression of BC; its inhibitors are emerging as a potent primary or adjuvant therapy. On the other hand, glucocorticoids (GCs) are already used as neo-adjuvant and adjuvant therapies to treat various cancers with remarkable effects to induce apoptosis in leukemia and lymphoma. However, GCs unexpectedly promote cancer cell survival and induce chemo-resistance in BC. To understand this unique transcriptional interplay in BC, in this review we discuss the functions of NFkB and GR in BC development and progression by emphasizing their cross talk at cell signaling and protein interaction levels; and the future perspectives are proposed for the development of new therapeutic approaches for BC based on these signaling pathways.
乳腺癌（BC）是一种侵袭性和高死亡率的癌症，可以根据基因表达谱分为五个分子亚型。这种极端的异质性给理解和治疗 BC 带来了困难。在许多风险因素中，炎症在 BC 的进展和复发中起着因果作用，其中 NFkB 和糖皮质激素受体（GR）是调节炎症的关键转录因子。NFkB 通常是促炎的，GR 是抗炎的，构成了调节中的阴阳模式。因此，这两个转录因子之间的串扰在决定 BC 细胞的存活或凋亡方面发挥着更重要的作用。NFkB 广泛参与 BC 的发生和发展；其抑制剂正作为一种有效的主要或辅助治疗方法出现。另一方面，糖皮质激素（GCs）已被用作新辅助和辅助治疗各种癌症的药物，在诱导白血病和淋巴瘤细胞凋亡方面具有显著效果。然而，GCs 出人意料地促进了 BC 中癌细胞的存活，并诱导了化疗耐药性。为了了解 BC 中这种独特的转录相互作用，在这篇综述中，我们通过强调 NFkB 和 GR 在细胞信号转导和蛋白质相互作用水平上的相互作用，讨论了它们在 BC 发生和发展中的功能；并为基于这些信号通路的 BC 新治疗方法的发展提出了未来的展望。
