p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells
Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2007-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607800030 |
| _version_ | 1811329073332355072 |
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| author | Haifeng Jin Yanglin Pan Lina Zhao Huihong Zhai Xiaohua Li Li Sun Lijie He Yu Chen Liu Hong Yulei Du Daiming Fan |
| author_facet | Haifeng Jin Yanglin Pan Lina Zhao Huihong Zhai Xiaohua Li Li Sun Lijie He Yu Chen Liu Hong Yulei Du Daiming Fan |
| author_sort | Haifeng Jin |
| collection | DOAJ |
| description | Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Δp75NTR) showed that the death domain transduced antiproliferative activity in a ligandindependent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer. |
| first_indexed | 2024-04-13T15:37:22Z |
| format | Article |
| id | doaj.art-3b7fd0b79d9443d0a74bcb0ca617b620 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T15:37:22Z |
| publishDate | 2007-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-3b7fd0b79d9443d0a74bcb0ca617b6202022-12-22T02:41:14ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-06-019647147810.1593/neo.07175p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer CellsHaifeng Jin0Yanglin Pan1Lina Zhao2Huihong Zhai3Xiaohua Li4Li Sun5Lijie He6Yu Chen7Liu Hong8Yulei Du9Daiming Fan10State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Van, Shaanxi Province 710032, ChinaIdentifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Δp75NTR) showed that the death domain transduced antiproliferative activity in a ligandindependent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.http://www.sciencedirect.com/science/article/pii/S1476558607800030Proliferationp75NTRcell cyclegastric cancergrowth |
| spellingShingle | Haifeng Jin Yanglin Pan Lina Zhao Huihong Zhai Xiaohua Li Li Sun Lijie He Yu Chen Liu Hong Yulei Du Daiming Fan p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells Neoplasia: An International Journal for Oncology Research Proliferation p75NTR cell cycle gastric cancer growth |
| title | p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells |
| title_full | p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells |
| title_fullStr | p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells |
| title_full_unstemmed | p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells |
| title_short | p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells |
| title_sort | p75 neurotrophin receptor suppresses the proliferation of human gastric cancer cells |
| topic | Proliferation p75NTR cell cycle gastric cancer growth |
| url | http://www.sciencedirect.com/science/article/pii/S1476558607800030 |
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