HOXB7 as a Prognostic Factor and Mediator of Colorectal Cancer Progression
| Autor: | Xiu-Wu Bian, Jian Yuan, Yanqing Ding, Dan Jiang, Yongjian Deng, Yan-Mei Cui, Wenting Liao, Cui-Min Chen, Xi-Wen Shi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research Proliferation index MAP Kinase Signaling System Mice Nude Mice Cyclin D1 Downregulation and upregulation Cell Line Tumor Biomarkers Tumor Animals Humans Medicine Protein kinase B PI3K/AKT/mTOR pathway Aged Cell Proliferation Aged 80 and over Homeodomain Proteins business.industry Cell growth Cancer Middle Aged medicine.disease Oncology Tumor progression Immunology Disease Progression Cancer research Female Colorectal Neoplasms business |
| Zdroj: | Clinical Cancer Research. 17:3569-3578 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-10-2533 |
| Popis: | Purpose: This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC). Experimental Design: The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways. Results: HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G0–G1 to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G1–S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity. Conclusion: Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC. Clin Cancer Res; 17(11); 3569–78. ©2011 AACR. |
| Databáze: | OpenAIRE |
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