Estrogens and IL-12 play a pivotal role in the development and progression of non-small-cell lung cancer (NSCLC); at the same time, estrogen receptor β2 and (interleukin-12 receptor β2)IL-12Rβ2 are their important receptors, respectively. With the functions of ERβ2 and IL-12Rβ2 explored further in NSCLC, some questions on the relation between ERβ2 and IL-12Rβ2 expression need to be solved. In this study, our aim is to elucidate relationship and roles of ERβ2 and IL-12Rβ2 in NSCLC. The expression of estrogen receptors β2 and IL-12Rβ2 was confirmed by Western blot and RT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics was evaluated by Mann-Whitney and Kruskal-Wallis test. Using Kaplan-Meier plots and Cox proportional hazard models analyses, overall survival (OS) was evaluated. In contrast to benign pulmonary, ERβ2 and IL-12Rβ2 were over-expressed in NSCLC (p = 0.000). IHC results showed significant correlation between ERβ2 and IL-12Rβ2 (R = 0.382, p = 0.005). By analyzing the relation between ERβ2, IL-12Rβ2 mRNA expression levels and clinical characteristics, it was revealed that ERβ2 and IL-12Rβ2 were significant correlated with regional lymph node metastasis, T stage and clinical stage (p = 0.000/0.000; 0.001/0.000; 0.031/0.003 respectively), and both protein expression levels were lower with TNM stage being higher. In a Kaplan-Meier analysis, compared to both ERβ2 and IL-12Rβ2 or one low expression, high expression levels of ERβ2 and IL-12Rβ2 were identified in a group of patients with the longest overall survival (OS). Cox proportional hazard models revealed that ERβ2 and IL-12Rβ5 had longer OS. This is the first study to uncover that both ERβ2 and IL-12Rβ2 were over-expressed and further show that they were co-expressed in NSCLC. Moreover, we found that high expression levels of ERβ2 and IL-12Rβ2 may be positively correlated with OS and have prognostic values for the progression of NSCLC.
The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.
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