Potential Oncogenic Role of the Papillary Renal Cell Carcinoma Gene in Non-Small Cell Lung Cancers
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Purpose: Papillary renal cell carcinoma (PRCC) gene, which located in 1q23.1, is recurrently amplified in non-small cell lungcancer (NSCLC). However, it is unknown whether PRCC is overexpressed in primary NSCLCs and whether PRCC overexpressioncontributes to lung tumorigenesis. In this study, we aimed to identify the profiles of PRCC expression in Korean NSCLC patientsand to elucidate the role of PRCC overexpression on lung tumorigenesis. Materials and Methods: We performed immunohistochemistry analysis with a tissue array containing 161 primary NSCLCs. Smallinterfering RNA targeting PRCC (siPRCC) was transfected into two lung cancer cell lines (NCI-H358 and A549), after which tumorgrowth, migration, and invasion were observed. Expressions of cell proliferation-, cell cycle-, and metastasis-related moleculeswere examined by Western blot analysis. We also explored the in vivo effect of PRCC silencing. Results: PRCC overexpression was recurrently observed in NSCLCs (95/161, 59%). After siPRCC treatment, tumor cell proliferation,colony formation, and anchorage independent growth were significantly reduced (p<0.001 for all three effects). Migrationand invasiveness were also significantly repressed (p<0.001 for both effects). Reflecting cell proliferation, cell cycle, and metastasis,the expressions of Ki67, cyclin D1, AKT-1, pAKT, NF-kB p65, vimentin and CXCL-12 were found to be downregulated. Throughmouse xenograft analysis, we confirmed that PRCC silencing significantly repressed a xenograft tumor mass in vivo (p<0.001). Conclusion: The present data provide evidence that PRCC overexpression is involved in the tumorigenesis and progression oflung cancer.
Abstract
Purpose: Papillary renal cell carcinoma (PRCC) gene, which located in 1q23.1, is recurrently amplified in non-small cell lungcancer (NSCLC). However, it is unknown whether PRCC is overexpressed in primary NSCLCs and whether PRCC overexpressioncontributes to lung tumorigenesis. In this study, we aimed to identify the profiles of PRCC expression in Korean NSCLC patientsand to elucidate the role of PRCC overexpression on lung tumorigenesis. Materials and Methods: We performed immunohistochemistry analysis with a tissue array containing 161 primary NSCLCs. Smallinterfering RNA targeting PRCC (siPRCC) was transfected into two lung cancer cell lines (NCI-H358 and A549), after which tumorgrowth, migration, and invasion were observed. Expressions of cell proliferation-, cell cycle-, and metastasis-related moleculeswere examined by Western blot analysis. We also explored the in vivo effect of PRCC silencing. Results: PRCC overexpression was recurrently observed in NSCLCs (95/161, 59%). After siPRCC treatment, tumor cell proliferation,colony formation, and anchorage independent growth were significantly reduced (p<0.001 for all three effects). Migrationand invasiveness were also significantly repressed (p<0.001 for both effects). Reflecting cell proliferation, cell cycle, and metastasis,the expressions of Ki67, cyclin D1, AKT-1, pAKT, NF-kB p65, vimentin and CXCL-12 were found to be downregulated. Throughmouse xenograft analysis, we confirmed that PRCC silencing significantly repressed a xenograft tumor mass in vivo (p<0.001). Conclusion: The present data provide evidence that PRCC overexpression is involved in the tumorigenesis and progression oflung cancer.
참고문헌 (21)
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