Fazilaty Hassan, Gardaneh Mossa, Akbari Parvin, Zekri Ali, Behnam Babak
Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Cancer Microenviron. 2016 Apr;9(1):71-4. doi: 10.1007/s12307-015-0176-8. Epub 2015 Sep 28.
Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. SLUG and SOX9 transcription factors play essential roles in induction and maintenance of tumor initiating capacity in breast cancer cells. On the other hand, Tenascin-C and Periostin are crucial factors in metastatic niche that support tumor initiating capability in breast cancer. In this study, regulatory effect of SLUG and SOX9 transcription factors on the expression of Tenascin-C and Periostin was examined. SLUG and SOX9 were overexpressed and knocked-down in MCF7 and MDA-MB-231 cells, respectively. The cells as little and highly invasive breast cancer-derived cells were infected by inducing and shRNA lentivirus constructs. Then, Tenascin-C and Periostin as well as SLUG and SOX9 expression levels were measured in the cells via Real-Time PCR. Simultaneous overexpression of SLUG and SOX9 significantly induced Tenascin-C and Periostin expression. SLUG and SOX9 knock-down also significantly reduced the expression of Tenascin-C and Periostin. In this analysis Periostin showed the most deviation in both up- and down-regulation levels. This regulatory effect might shed light to a crosstalk between factors involved in the tumor initiating capacity and metastatic niche of the breast cancer.
肿瘤起始细胞的存在和合适的微环境对于转移定植至关重要。SLUG和SOX9转录因子在乳腺癌细胞肿瘤起始能力的诱导和维持中发挥着重要作用。另一方面，肌腱蛋白-C和骨膜蛋白是转移微环境中的关键因子，可支持乳腺癌的肿瘤起始能力。在本研究中，检测了SLUG和SOX9转录因子对肌腱蛋白-C和骨膜蛋白表达的调节作用。分别在MCF7和MDA-MB-231细胞中过表达和敲低SLUG和SOX9。通过诱导型和shRNA慢病毒构建体感染作为低侵袭性和高侵袭性乳腺癌来源细胞的这些细胞。然后，通过实时PCR测量细胞中肌腱蛋白-C、骨膜蛋白以及SLUG和SOX9的表达水平。SLUG和SOX9的同时过表达显著诱导了肌腱蛋白-C和骨膜蛋白的表达。SLUG和SOX9的敲低也显著降低了肌腱蛋白-C和骨膜蛋白的表达。在该分析中，骨膜蛋白在上调和下调水平上均表现出最大差异。这种调节作用可能为乳腺癌肿瘤起始能力和转移微环境中相关因子之间的串扰提供线索。
