Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway in Human Lung Adenocarcinoma A549 Cells
Background and objective It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis. COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway. Inhibiting the expression of COX-2 can prevent the developmen...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | zho |
| Published: |
Chinese Anti-Cancer Association; Chinese Antituberculosis Association
2013-04-01
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| Series: | Chinese Journal of Lung Cancer |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.3779/j.issn.1009-3419.2013.04.01 |
| _version_ | 1818020515064840192 |
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| author | Jian CUI Yubo YAN Yanzhong XIN Jiyao LI Qing DONG Guibin ZHAO Jingquan HAN Shouqiang CAO |
| author_facet | Jian CUI Yubo YAN Yanzhong XIN Jiyao LI Qing DONG Guibin ZHAO Jingquan HAN Shouqiang CAO |
| author_sort | Jian CUI |
| collection | DOAJ |
| description | Background and objective It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis. COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway. Inhibiting the expression of COX-2 can prevent the development of lung cancer. The aim fo this study is to investigate whether the epidermal growth factor (EGF) can stimulate the signal transducers and activators of transcription 5 (STAT5) as well as to discover the effects of the STAT5 signaling pathway on the COX-2 in human lung adenocarcinoma A549 cells. Methods The phenomenon of STAT5 activation stimulated by the EGF was assayed through immunofluorescence and Western blot. The adenovirus containing the wild-type (WT)-STAT5 (AdWT-STAT5) plasmid, dominant-negative (DN)-STAT5 (Ad-CMV5Stat5aΔ740) plasmid, and STAT5 siRNA were transfected into A549 cells. The latter two groups were stimulated using EGF. Reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of COX-2. Results STAT5 was not activated in A549 cells in vitro. EGF stimulation significantly increased the level of the p-STAT5 protein and induces the shuttling of p-STAT5 from the cytoplasm into the nucleus. STAT5 activation was crucial for the COX-2 expression induced by the EGF. STAT5 was required for COX-2 expression, but can mediated the effects of the COX-2 expression through pathways that were independent of transcriptional activation. Conclusion COX-2 expression is dependent on STAT5 phosphorylation. A second pathway does not require STAT5 phosphorylation. |
| first_indexed | 2024-04-14T08:06:19Z |
| format | Article |
| id | doaj.art-827e4e30e2b8402796d7b1bc53620ae9 |
| institution | Directory Open Access Journal |
| issn | 1009-3419 1999-6187 |
| language | zho |
| last_indexed | 2024-04-14T08:06:19Z |
| publishDate | 2013-04-01 |
| publisher | Chinese Anti-Cancer Association; Chinese Antituberculosis Association |
| record_format | Article |
| series | Chinese Journal of Lung Cancer |
| spelling | doaj.art-827e4e30e2b8402796d7b1bc53620ae92022-12-22T02:04:43ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872013-04-0116416917610.3779/j.issn.1009-3419.2013.04.01Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 CellsJian CUIYubo YANYanzhong XINJiyao LIQing DONGGuibin ZHAOJingquan HANShouqiang CAOBackground and objective It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis. COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway. Inhibiting the expression of COX-2 can prevent the development of lung cancer. The aim fo this study is to investigate whether the epidermal growth factor (EGF) can stimulate the signal transducers and activators of transcription 5 (STAT5) as well as to discover the effects of the STAT5 signaling pathway on the COX-2 in human lung adenocarcinoma A549 cells. Methods The phenomenon of STAT5 activation stimulated by the EGF was assayed through immunofluorescence and Western blot. The adenovirus containing the wild-type (WT)-STAT5 (AdWT-STAT5) plasmid, dominant-negative (DN)-STAT5 (Ad-CMV5Stat5aΔ740) plasmid, and STAT5 siRNA were transfected into A549 cells. The latter two groups were stimulated using EGF. Reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of COX-2. Results STAT5 was not activated in A549 cells in vitro. EGF stimulation significantly increased the level of the p-STAT5 protein and induces the shuttling of p-STAT5 from the cytoplasm into the nucleus. STAT5 activation was crucial for the COX-2 expression induced by the EGF. STAT5 was required for COX-2 expression, but can mediated the effects of the COX-2 expression through pathways that were independent of transcriptional activation. Conclusion COX-2 expression is dependent on STAT5 phosphorylation. A second pathway does not require STAT5 phosphorylation.http://dx.doi.org/10.3779/j.issn.1009-3419.2013.04.01STAT5COX-2Lung neoplasmsA549EGF |
| spellingShingle | Jian CUI Yubo YAN Yanzhong XIN Jiyao LI Qing DONG Guibin ZHAO Jingquan HAN Shouqiang CAO Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway in Human Lung Adenocarcinoma A549 Cells Chinese Journal of Lung Cancer STAT5 COX-2 Lung neoplasms A549 EGF |
| title | Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 Cells |
| title_full | Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 Cells |
| title_fullStr | Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 Cells |
| title_full_unstemmed | Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 Cells |
| title_short | Mechanisms of EGF Regulation of COX-2 Through the STAT5 Signaling Pathway
in Human Lung Adenocarcinoma A549 Cells |
| title_sort | mechanisms of egf regulation of cox 2 through the stat5 signaling pathway
in human lung adenocarcinoma a549 cells |
| topic | STAT5 COX-2 Lung neoplasms A549 EGF |
| url | http://dx.doi.org/10.3779/j.issn.1009-3419.2013.04.01 |
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