GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer
<p>Abstract</p> <p>Objectives</p> <p>G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that GPR30 expression is asso...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-11-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | http://www.ovarianresearch.com/content/5/1/35 |
| _version_ | 1797971458034499584 |
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| author | Fujiwara Satoe Terai Yoshito Kawaguchi Hiroshi Takai Masaaki Yoo Saha Tanaka Yoshimichi Tanaka Tomohito Tsunetoh Satoshi Sasaki Hiroshi Kanemura Masanori Tanabe Akiko Yamashita Yoshiki Ohmichi Masahide |
| author_facet | Fujiwara Satoe Terai Yoshito Kawaguchi Hiroshi Takai Masaaki Yoo Saha Tanaka Yoshimichi Tanaka Tomohito Tsunetoh Satoshi Sasaki Hiroshi Kanemura Masanori Tanabe Akiko Yamashita Yoshiki Ohmichi Masahide |
| author_sort | Fujiwara Satoe |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Objectives</p> <p>G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that GPR30 expression is associated with a poor prognosis, and that this is due to the GPR30-mediated transactivation of the EGFR in breast cancer. However, the biological contribution of GPR30 in ovarian cancer remains unclear. The purpose of this study was to elucidate the relationships between GPR30 expression and the clinicopathological findings, and to determine how the signaling cascade influences the prognosis of ovarian cancer.</p> <p>Methods</p> <p>The expression levels of GPR30, EGFR, ERα, and ERβ were analyzed using an immunohistochemical analysis, and their correlations with the clinicopathological features were examined in 10 patients with borderline malignant tumors and 152 patients with epithelial ovarian cancer. We also examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis.</p> <p>Results</p> <p>The GPR30 expression in ovarian carcinomas was significantly higher than that in borderline malignancies (p=0.0016), and was not associated with the expression of the EGFR, ERα, or ERβ. The expression of GPR30 in clear cell carcinomas was significantly lower than that in other subtypes of cancer (P <; 0.001). The expression of both GPR30 and EGFR was significantly associated with a poor prognosis in terms of the progression-free survival rate. The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p <; 0.05) and inhibited by a Src family kinase inhibitor.</p> <p>Conclusion</p> <p>The expression of both GPR30 and EGFR is associated with a poor outcome in ovarian cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells. The regulation of GPR30 might be a potentially useful new therapeutic target in ovarian cancer.</p> |
| first_indexed | 2024-04-11T03:31:51Z |
| format | Article |
| id | doaj.art-fa92a0a78eac46ffa768b4884d791ed4 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T03:31:51Z |
| publishDate | 2012-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-fa92a0a78eac46ffa768b4884d791ed42023-01-02T06:17:53ZengBMCJournal of Ovarian Research1757-22152012-11-01513510.1186/1757-2215-5-35GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancerFujiwara SatoeTerai YoshitoKawaguchi HiroshiTakai MasaakiYoo SahaTanaka YoshimichiTanaka TomohitoTsunetoh SatoshiSasaki HiroshiKanemura MasanoriTanabe AkikoYamashita YoshikiOhmichi Masahide<p>Abstract</p> <p>Objectives</p> <p>G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that GPR30 expression is associated with a poor prognosis, and that this is due to the GPR30-mediated transactivation of the EGFR in breast cancer. However, the biological contribution of GPR30 in ovarian cancer remains unclear. The purpose of this study was to elucidate the relationships between GPR30 expression and the clinicopathological findings, and to determine how the signaling cascade influences the prognosis of ovarian cancer.</p> <p>Methods</p> <p>The expression levels of GPR30, EGFR, ERα, and ERβ were analyzed using an immunohistochemical analysis, and their correlations with the clinicopathological features were examined in 10 patients with borderline malignant tumors and 152 patients with epithelial ovarian cancer. We also examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis.</p> <p>Results</p> <p>The GPR30 expression in ovarian carcinomas was significantly higher than that in borderline malignancies (p=0.0016), and was not associated with the expression of the EGFR, ERα, or ERβ. The expression of GPR30 in clear cell carcinomas was significantly lower than that in other subtypes of cancer (P <; 0.001). The expression of both GPR30 and EGFR was significantly associated with a poor prognosis in terms of the progression-free survival rate. The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p <; 0.05) and inhibited by a Src family kinase inhibitor.</p> <p>Conclusion</p> <p>The expression of both GPR30 and EGFR is associated with a poor outcome in ovarian cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells. The regulation of GPR30 might be a potentially useful new therapeutic target in ovarian cancer.</p>http://www.ovarianresearch.com/content/5/1/35G protein-coupled receptor 30GPR307-transmembrane estrogen receptorEGFRAktERα; Clear cell carcinomasPrognostic factor |
| spellingShingle | Fujiwara Satoe Terai Yoshito Kawaguchi Hiroshi Takai Masaaki Yoo Saha Tanaka Yoshimichi Tanaka Tomohito Tsunetoh Satoshi Sasaki Hiroshi Kanemura Masanori Tanabe Akiko Yamashita Yoshiki Ohmichi Masahide GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer Journal of Ovarian Research G protein-coupled receptor 30 GPR30 7-transmembrane estrogen receptor EGFR Akt ERα; Clear cell carcinomas Prognostic factor |
| title | GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer |
| title_full | GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer |
| title_fullStr | GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer |
| title_full_unstemmed | GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer |
| title_short | GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer |
| title_sort | gpr30 regulates the egfr akt cascade and predicts lower survival in patients with ovarian cancer |
| topic | G protein-coupled receptor 30 GPR30 7-transmembrane estrogen receptor EGFR Akt ERα; Clear cell carcinomas Prognostic factor |
| url | http://www.ovarianresearch.com/content/5/1/35 |
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