Papanastasiou Anastasios D, Sirinian Chaido, Plakoula Eva, Zolota Vassiliki, Zarkadis Ioannis K, Kalofonos Haralabos P
Clinical and Molecular Oncology Laboratory, Division of Oncology, School of Medicine, University of Patras, 26504, Greece.
Clinical and Molecular Oncology Laboratory, Division of Oncology, School of Medicine, University of Patras, 26504, Greece.
Cancer Genet. 2017 Oct;216-217:61-66. doi: 10.1016/j.cancergen.2017.07.004. Epub 2017 Jul 26.
Breast cancer is the most common malignancy, affecting one in eight women in North America and Europe. The human epidermal growth factor receptor (EGFR) protein comprises a major determinant of normal development but also cancer. RANK receptor (Receptor Activator of Nuclear factor-κB) is a tumor necrosis superfamily member and a binding partner for RANKL, which was recently implicated in breast cancer initiation, progression and metastasis. Here we provide preliminary evidence of a possible interplay between RANK and EGFR signaling in breast cancer. TCGA (cancergenome.nih.gov) publicly available data for EGFR and TNFRSF11A (RANK) genes from breast cancer patients and breast cancer cell lines were retrieved and analyzed. RANK mRNA showed a statistically significant positive correlation (p <0.001) with the mRNA and protein expression of EGFR, but not with ERBB2/3/4. Further analyses of survival data of a group of breast cancer patients (n = 248) from TCGA, revealed an EGFR/RANK subpopulation that showed a statistically significant (p = 0.001) reduced overall survival when compared to EGFR/RANK group of patients. Finally, EGFR and RANK combinatorial in vitro analyses revealed a significant upregulation of AKT and ERK signaling after EGF stimulation in cell lines and also an increase of breast cancer cell invasiveness.
乳腺癌是最常见的恶性肿瘤，在北美和欧洲，每八名女性中就有一人受其影响。人表皮生长因子受体（EGFR）蛋白是正常发育的主要决定因素，也是癌症的主要决定因素。RANK受体（核因子κB受体激活剂）是肿瘤坏死超家族成员，也是RANKL的结合伴侣，RANKL最近被认为与乳腺癌的发生、发展和转移有关。在这里，我们提供了RANK和EGFR信号在乳腺癌中可能相互作用的初步证据。从癌症基因组.nih.gov网站检索并分析了来自乳腺癌患者和乳腺癌细胞系的EGFR和TNFRSF11A（RANK）基因的公开可用数据。RANK mRNA与EGFR的mRNA和蛋白表达呈统计学显著正相关（p<0.001），但与ERBB2/3/4无相关性。对来自TCGA的一组乳腺癌患者（n = 248）的生存数据进行进一步分析，发现与EGFR/RANK患者组相比，EGFR/RANK亚组的总生存率有统计学显著降低（p = 0.001）。最后，EGFR和RANK的体外联合分析显示，在细胞系中，EGF刺激后AKT和ERK信号显著上调，同时乳腺癌细胞的侵袭性增加。
