Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR
<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) has been reported to downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has any effect on EGFR expression has not been elucidated. Our previous studies have found an...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-09-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/10/1/116 |
| _version_ | 1818520524215549952 |
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| author | Shin Dong M Zhang Hongzheng Huang Donghai Su Ling Wang Dongsheng Chen Zhuo G |
| author_facet | Shin Dong M Zhang Hongzheng Huang Donghai Su Ling Wang Dongsheng Chen Zhuo G |
| author_sort | Shin Dong M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) has been reported to downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has any effect on EGFR expression has not been elucidated. Our previous studies have found an inverse correlation between EGFR and E-cad expression in tissue specimens of squamous cell carcinoma of the head and neck (SCCHN). To understand the biological mechanisms underlying this clinical observation, we knocked down E-cad expression utilizing E-cad siRNA in four SCCHN cell lines.</p> <p>Results</p> <p>It was observed that downregulation of E-cad upregulated EGFR expression compared with control siRNA-transfected cells after 72 hours. Cellular membrane localization of EGFR was also increased. Consequently, downstream signaling molecules of the EGFR signaling pathway, p-AKT, and p-ERK, were increased at 72 hours after the transfection with E-cad siRNA. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed EGFR mRNA was upregulated by E-cad siRNA as early as 24 hours. In addition, RT-PCR revealed this upregulation was due to the increase of EGFR mRNA stability, but not protein stability. Sulforhodamine B (SRB) assay indicated growth of E-cad knocked down cells was enhanced up to 2-fold more than that of control siRNA-transfected cells at 72-hours post-transfection. The effect of E-cad reduction on cell proliferation was blocked by treating the E-cad siRNA-transfected cells with 1 μM of the EGFR-specific tyrosine kinase inhibitor erlotinib.</p> <p>Conclusion</p> <p>Our results suggest for the first time that reduction of E-cad results in upregulation of EGFR transcriptionally. It also suggests that loss of E-cad may induce proliferation of SCCHN by activating EGFR and its downstream signaling pathways.</p> |
| first_indexed | 2024-12-11T01:38:39Z |
| format | Article |
| id | doaj.art-4fb8f1b297c04ee58cbda4fb085a2584 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-11T01:38:39Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-4fb8f1b297c04ee58cbda4fb085a25842022-12-22T01:25:07ZengBMCMolecular Cancer1476-45982011-09-0110111610.1186/1476-4598-10-116Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFRShin Dong MZhang HongzhengHuang DonghaiSu LingWang DongshengChen Zhuo G<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) has been reported to downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has any effect on EGFR expression has not been elucidated. Our previous studies have found an inverse correlation between EGFR and E-cad expression in tissue specimens of squamous cell carcinoma of the head and neck (SCCHN). To understand the biological mechanisms underlying this clinical observation, we knocked down E-cad expression utilizing E-cad siRNA in four SCCHN cell lines.</p> <p>Results</p> <p>It was observed that downregulation of E-cad upregulated EGFR expression compared with control siRNA-transfected cells after 72 hours. Cellular membrane localization of EGFR was also increased. Consequently, downstream signaling molecules of the EGFR signaling pathway, p-AKT, and p-ERK, were increased at 72 hours after the transfection with E-cad siRNA. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed EGFR mRNA was upregulated by E-cad siRNA as early as 24 hours. In addition, RT-PCR revealed this upregulation was due to the increase of EGFR mRNA stability, but not protein stability. Sulforhodamine B (SRB) assay indicated growth of E-cad knocked down cells was enhanced up to 2-fold more than that of control siRNA-transfected cells at 72-hours post-transfection. The effect of E-cad reduction on cell proliferation was blocked by treating the E-cad siRNA-transfected cells with 1 μM of the EGFR-specific tyrosine kinase inhibitor erlotinib.</p> <p>Conclusion</p> <p>Our results suggest for the first time that reduction of E-cad results in upregulation of EGFR transcriptionally. It also suggests that loss of E-cad may induce proliferation of SCCHN by activating EGFR and its downstream signaling pathways.</p>http://www.molecular-cancer.com/content/10/1/116 |
| spellingShingle | Shin Dong M Zhang Hongzheng Huang Donghai Su Ling Wang Dongsheng Chen Zhuo G Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR Molecular Cancer |
| title | Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR |
| title_full | Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR |
| title_fullStr | Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR |
| title_full_unstemmed | Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR |
| title_short | Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR |
| title_sort | downregulation of e cadherin enhances proliferation of head and neck cancer through transcriptional regulation of egfr |
| url | http://www.molecular-cancer.com/content/10/1/116 |
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