Epithelial cell transforming sequence 2 in human oral cancer.
BACKGROUND: Epithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor for Rho family GTPase, which has been implicated in the malignant phenotype of human cancers. Little is known about the effect of a high level of ECT2 in regulating oral cancer cell behavior. In this s...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2993930?pdf=render |
| _version_ | 1828476299506614272 |
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| author | Manabu Iyoda Atsushi Kasamatsu Takashi Ishigami Dai Nakashima Yosuke Endo-Sakamoto Katsunori Ogawara Masashi Shiiba Hideki Tanzawa Katsuhiro Uzawa |
| author_facet | Manabu Iyoda Atsushi Kasamatsu Takashi Ishigami Dai Nakashima Yosuke Endo-Sakamoto Katsunori Ogawara Masashi Shiiba Hideki Tanzawa Katsuhiro Uzawa |
| author_sort | Manabu Iyoda |
| collection | DOAJ |
| description | BACKGROUND: Epithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor for Rho family GTPase, which has been implicated in the malignant phenotype of human cancers. Little is known about the effect of a high level of ECT2 in regulating oral cancer cell behavior. In this study, we investigated the involvement of ECT2 in oral squamous cell carcinoma (OSCC). METHODOLOGY/PRINCIPAL FINDINGS: We analyzed ECT2 expression in OSCC-derived cell lines and primary OSCCs compared with matched normal tissue (n = 96) by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. We then evaluated the correlation between the ECT2 expression status in primary OSCCs and the clinicopathological features. ECT2 expression was significantly up-regulated in OSCCs in vitro and in vivo (p<0.05). Among the clinical variables analyzed, higher ECT2 expression also was associated with the TNM stage grading (p<0.05). When we performed functional analyses of ECT2 in OSCC-derived cells using the shRNA system, the cellular proliferation of the ECT2 knockdown cells decreased significantly compared with the control cells (p<0.05). Cell cycle analysis by flow cytometry showed arrest of cell cycle progression at the G1 phase in the ECT2 knockdown cells. We also found up-regulation of the Cip/Kip family of the cyclin-dependent kinase inhibitors, p21(cip1) and p27(kip1), and down-regulation of cyclin D1, cyclin E, and CDK4. These data suggested that the elevated Cip/Kip family induced inhibition of the cyclin D1-CDK complex activity leading to cell cycle arrest at the G1 phase. CONCLUSIONS/SIGNIFICANCE: Our results proposed for the first time that ECT2 is an indicator of cellular proliferation in OSCCs and that ECT2 might be a potential therapeutic target for the development of new treatments for OSCCs. |
| first_indexed | 2024-12-11T06:26:45Z |
| format | Article |
| id | doaj.art-64ed3b17819c42b393468b2a22fb55d8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:26:45Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-64ed3b17819c42b393468b2a22fb55d82022-12-22T01:17:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-01511e1408210.1371/journal.pone.0014082Epithelial cell transforming sequence 2 in human oral cancer.Manabu IyodaAtsushi KasamatsuTakashi IshigamiDai NakashimaYosuke Endo-SakamotoKatsunori OgawaraMasashi ShiibaHideki TanzawaKatsuhiro UzawaBACKGROUND: Epithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor for Rho family GTPase, which has been implicated in the malignant phenotype of human cancers. Little is known about the effect of a high level of ECT2 in regulating oral cancer cell behavior. In this study, we investigated the involvement of ECT2 in oral squamous cell carcinoma (OSCC). METHODOLOGY/PRINCIPAL FINDINGS: We analyzed ECT2 expression in OSCC-derived cell lines and primary OSCCs compared with matched normal tissue (n = 96) by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. We then evaluated the correlation between the ECT2 expression status in primary OSCCs and the clinicopathological features. ECT2 expression was significantly up-regulated in OSCCs in vitro and in vivo (p<0.05). Among the clinical variables analyzed, higher ECT2 expression also was associated with the TNM stage grading (p<0.05). When we performed functional analyses of ECT2 in OSCC-derived cells using the shRNA system, the cellular proliferation of the ECT2 knockdown cells decreased significantly compared with the control cells (p<0.05). Cell cycle analysis by flow cytometry showed arrest of cell cycle progression at the G1 phase in the ECT2 knockdown cells. We also found up-regulation of the Cip/Kip family of the cyclin-dependent kinase inhibitors, p21(cip1) and p27(kip1), and down-regulation of cyclin D1, cyclin E, and CDK4. These data suggested that the elevated Cip/Kip family induced inhibition of the cyclin D1-CDK complex activity leading to cell cycle arrest at the G1 phase. CONCLUSIONS/SIGNIFICANCE: Our results proposed for the first time that ECT2 is an indicator of cellular proliferation in OSCCs and that ECT2 might be a potential therapeutic target for the development of new treatments for OSCCs.http://europepmc.org/articles/PMC2993930?pdf=render |
| spellingShingle | Manabu Iyoda Atsushi Kasamatsu Takashi Ishigami Dai Nakashima Yosuke Endo-Sakamoto Katsunori Ogawara Masashi Shiiba Hideki Tanzawa Katsuhiro Uzawa Epithelial cell transforming sequence 2 in human oral cancer. PLoS ONE |
| title | Epithelial cell transforming sequence 2 in human oral cancer. |
| title_full | Epithelial cell transforming sequence 2 in human oral cancer. |
| title_fullStr | Epithelial cell transforming sequence 2 in human oral cancer. |
| title_full_unstemmed | Epithelial cell transforming sequence 2 in human oral cancer. |
| title_short | Epithelial cell transforming sequence 2 in human oral cancer. |
| title_sort | epithelial cell transforming sequence 2 in human oral cancer |
| url | http://europepmc.org/articles/PMC2993930?pdf=render |
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