Down-regulation of CIT can inhibit the growth of human bladder cancer cells - 11/02/20
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| pages | 8 |
| Iconographies | 6 |
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| Autres | 0 |
Graphical abstract |
Highlights |
• | Overexpression of CIT is found in tumor tissues in various cancer patients. |
• | We found higher CIT level in bladder cancer tissues than normal bladder tissues. |
• | CIT knockdown represses cell growth and regulates cell cycle in vitro and in vivo. |
• | In summary, CIT may promote bladder cancer through regulation of cell cycle pathway. |
Abstract |
Objective |
Our study is to examine the citron rho-interacting, serine/threonine kinase 21 (CIT) in bladder cancer.
Methods |
We examined CIT level in human bladder cancer tissues by immunohistochemical staining. To explore the impact of CIT on cell proliferation and apoptosis, we down-regulated its expression in two human bladder cancer cell lines, 5367 and T24. We examined cell growth in 5367 and T24. We also performed in vivo analysis using T24 cells. We further used microarray expression profiling to investigate genes differentially expressed in T24 cells with CIT down-regulated.
Results |
In 100 human samples, CIT was expressed by only 2 of 30 (6.7 %) controls in bladder tissues, whereas by 64 of 70 (91.4 %) cancer patients in tumor tissues (p < 0.001). in vitro analysis demonstrated that CIT knockdown represses cell proliferation by 50 % in both cells and colony formation (77 ± 5 vs. 13 ± 2, p = 0.001 for T24, 58 ± 3 vs. 1 ± 1, p < 0.001 for 5637). We also found CIT knockdown could induce cell cycle arrest, and promote apoptosis in both cells. Tumor-volume monitoring and live in vivo bladder cancer imaging in human xenograft model confirmed that CIT knockdown reduces tumor volume (668.4 ± 333.0 vs. 305.7 ± 170.4 mm3, p = 0.02) and weight (0.27 ± 0.15 vs. 0.57 ± 0.32 g, p = 0.02). Microarray analysis revealed that CIT may regulate cell cycle signalling pathway through various cell cycle regulators.
Conclusions |
In summary, we provided clinical and experimental evidence that CIT may promote bladder cancer through regulation of cell cycle pathway.
Le texte complet de cet article est disponible en PDF.Keywords : Apoptosis, Bladder cancer cell, Citron rho-interacting, Serine/threonine kinase 21, Proliferation
Plan
Vol 124
Article 109830- avril 2020 Retour au numéro
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