Abstract
Protein kinase C epsilon (PKCε), an oncogene overexpressed in several human cancers, is involved in cell proliferation, migration, invasion, and survival. However, its roles in clear cell renal cell carcinoma (RCC) are unclear. This study aimed to investigate the functions of PKCε in RCC, especially in clear cell RCC, to determine the possibility of using it as a therapeutic target. By immunohistochemistry, we found that the expression of PKCε was up-regulated in RCCs and was associated with tumor Fuhrman grade and T stage in clear cell RCCs. Clone formation, wound healing, and Borden assays showed that down-regulating PKCε by RNA interference resulted in inhibition of the growth, migration, and invasion of clear cell RCC cell line 769P and, more importantly, sensitized cells to chemotherapeutic drugs as indicated by enhanced activity of caspase-3 in PKCε siRNA-transfected cells. These results indicate that the overexpression of PKCε is associated with an aggressive phenotype of clear cell RCC and may be a potential therapeutic target for this disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Antineoplastic Agents / pharmacology
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Biomarkers, Tumor / metabolism*
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Blotting, Western
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / metabolism*
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Carcinoma, Renal Cell / pathology
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Colony-Forming Units Assay
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Female
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Fluorouracil / pharmacology
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Gene Expression Regulation, Neoplastic
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Humans
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Immunoenzyme Techniques
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Indoles / pharmacology
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / metabolism*
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Kidney Neoplasms / pathology
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Male
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Middle Aged
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Neoplasm Grading
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Neoplasm Invasiveness
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Neoplasm Staging
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Prognosis
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Protein Kinase C-epsilon / antagonists & inhibitors
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Protein Kinase C-epsilon / genetics
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Protein Kinase C-epsilon / metabolism*
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Pyrroles / pharmacology
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Sunitinib
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Wound Healing
Substances
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Antimetabolites, Antineoplastic
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Antineoplastic Agents
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Biomarkers, Tumor
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Indoles
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Pyrroles
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RNA, Messenger
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RNA, Small Interfering
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Protein Kinase C-epsilon
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Caspase 3
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Fluorouracil
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Sunitinib