Down-regulation of CD74 inhibits growth and invasion in clear cell renal cell carcinoma through HIF-1α pathway
| Autor: | Haijian Zhang, Yuqian Zhao, Shiqi Ji, Zhixing Han, Xiao-Lin Su, Wenlong Cheng |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Urology Blotting Western Down-Regulation Mice Nude Antigens CD7 Cell Line Mice Western blot Cell Line Tumor Animals Humans Medicine Neoplasm Invasiveness Carcinoma Renal Cell Aged Cell Proliferation Aged 80 and over Mice Inbred BALB C biology medicine.diagnostic_test business.industry Cell growth Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays Kidney Neoplasms Clear cell renal cell carcinoma Oncology Hypoxia-inducible factors Cell culture Apoptosis Immunology biology.protein Cancer research Female RNA Interference business Platelet-derived growth factor receptor Immunostaining Signal Transduction |
| Zdroj: | Urologic Oncology: Seminars and Original Investigations. 32:153-161 |
| ISSN: | 1078-1439 |
| DOI: | 10.1016/j.urolonc.2012.09.013 |
| Popis: | Objectives To investigate the expression and function of CD74 in normal renal tissue and clear cell–renal cell carcinoma (ccRCC), as well as related renal tubule epithelial lines. We also analyzed the association between clinicopathological characteristics of ccRCCs and the expression levels of CD74. Methods Immunostaining of CD74 was performed in 107 patients' renal tissue and cell lines. We evaluated the association between clinicopathological characteristics of ccRCC and CD74 levels using image analysis. CD74 expression levels were also analyzed by Western blot. Lentivirus-mediated CD74 knockdown inhibited the growth and invasion, of ccRCC cell lines 786-O in vitro and in vivo. Cell proliferation, apoptosis, and invasion as well as HIF-1α pathway–related proteins, were estimated by Western blot. All experiments were repeated at least 3 times. Results Immunostaining and image analysis showed strong immunoreactions of CD74 in all patients' ccRCC tissue and malignant cell lines, while CD74 expression levels were associated with tumor grade ( P = 0.013). Western blot indicated that ccRCC tissue and malignant cell lines expressed higher levels of CD74 and hypoxia inducible factor 1α (HIF-1α) than adjacent normal renal tissue and normal cell HK-2. Vitro and vivo tests demonstrated that lentivirus-mediated CD74 knockdown inhibited the proliferation of ccRCC cell lines, induced G1/S arrest and apoptosis, and inhibited invasion. Inhibition of CD74 resulted in down-regulation of HIF-1α pathway proteins. Conclusions CD74 was overexpressed in human ccRCCs and associated with tumor grade, and inhibition of CD74 produced ccRCC proliferation arrest, induced apoptosis, and inhibited invasion, which impinged on HIF-1α pathway–related proteins. It might represent a potential therapeutic target for ccRCC. |
| Databáze: | OpenAIRE |
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