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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jiao, Xing-Yuan Chen, Zhen-Guang Feng, Ke Liu, Zhao-Guo Luo, Hong-He |
| Description | Author Affiliation: Liu ZG ( Department of General Thoracic Surgery, First Affiliated Hospital, SunYat sen University, Guangzhou, Guangdong 510089, P.R. China.); Jiao XY ( Organ Transplantation Center, First Affiliated Hospital, Sun YatSen University, Guangzhou, Guangdong 510080, P.R. China.); Chen ZG ( Department of General Thoracic Surgery, First Affiliated Hospital, SunYat sen University, Guangzhou, Guangdong 510089, P.R. China.); Feng K ( Department of General Thoracic Surgery, First Affiliated Hospital, SunYat sen University, Guangzhou, Guangdong 510089, P.R. China.); Luo HH ( Department of General Thoracic Surgery, First Affiliated Hospital, SunYat sen University, Guangzhou, Guangdong 510089, P.R. China.) |
| Abstract | Lung cancer is one of the most common types of cancer and is the leading cause of cancer-related mortality worldwide. Estrogens are known to be involved in the development and progression of non-small-cell lung cancer (NSCLC). These effects are initially mediated through binding of estrogen to estrogen receptors (ERs), in particular ERß2. Our preliminary studies demonstrated that ERß2 and interleukin-12 receptorß2 (IL-12Rß2) expression are correlated in NSCLC. The present study investigated the expression of these proteins in NSCLC cells and how changes in their expression affected cell proliferation and invasion. In addition, it aimed to explore whether p38 mitogen-activated protein kinase (p38MAPK) is involved in the regulation of IL-12Rß2 expression by ERß2. An immunocytochemical array was used to observe the distribution of ERß2 and IL-12Rß2. Co-immuoprecipitation was employed to observe the interaction between p38MAPK and IL-12Rß2, by varying the expression of ERß2 and p38MAPK. Western-blot analysis and reverse transcription-polymerase chain reaction assays were used to investigate the mechanism underlying ERß2 regulation of IL-12Rß2 expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, scratch wound healing and Transwell assays were used to investigate the impact of ERß2 on proliferative, invasive and migratory abilities of NSCLC cells. ERß2 was predominantly found in the cytoplasm and nucleus, whilst IL-12Rß2 was largely confined to the cytoplasm, although a degree of expression was observed in the nucleus. Compared with normal bronchial epithelial cells, IL-12Rß2 and ERß2 were overexpressed in the NSCLC cell groups. Coimmuoprecipitation demonstrated an interaction between p38MAPK and IL-12Rß2. ERß2 appeared to upregulate IL-12Rß2 expression and inhibition of p38MAPK attenuated this effect. ERß2 and IL-12Rß2 expression inhibited the proliferation, metastasis and invasion of NSCLC cell lines, but knockout of IL-12Rß2, even in the presence of ERß2, led to an increase in NSCLC cell proliferation and invasiveness. In conclusion, to the best of our knowledge this study is the first to demonstrate that IL-12Rß2 may be important in the mechanisms underlying ERß2 inhibition of NSCLC development, and that this interaction may be mediated via p38MAPK. |
| ISSN | 17912997 |
| e-ISSN | 17913004 |
| Journal | Molecular Medicine Reports |
| Issue Number | 1 |
| Volume Number | 12 |
| Language | English |
| Publisher | Spandidos Publications |
| Publisher Date | 2015-07-01 |
| Publisher Place | Greece |
| Access Restriction | Open |
| Subject Keyword | Epithelial Cells Metabolism Estrogen Receptor Beta Genetics Gene Expression Regulation, Neoplastic Receptors, Interleukin-12 P38 Mitogen-activated Protein Kinases Bronchi Pathology Cell Line, Tumor Cell Movement Cell Nucleus Cell Proliferation Cytoplasm Diffusion Chambers, Culture Protein Binding Protein Isoforms Rna, Small Interfering Antagonists & Inhibitors Signal Transduction Discipline Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Biochemistry Molecular Biology Cancer Research Molecular Medicine Oncology |
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