The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma

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.

Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

“…PRKCε was also found to be more abundant in some highly metastatic OS cells at the protein level, and in some MD-OS tumors at the transcript level. Although PRKCε is known to support migration of other cell types [89,96,98,117,118], there was no evidence to support a role for PRKCε in the migration of M132 osteosarcoma cells in this study. This may indicate that the aberrant expression of PRKCε and its network in vitro and in vivo is related to a bystander effect, or that the functional relevance of this aberrant expression has not yet been elucidated.…”

“…Literature searches of the genes contained in the highly significant network results showed that PRKCε has been characterized in progression of prostate [82,83,84,85,86,87], breast [88,89], and renal cancers [90], as well as tumorigenesis of squamous cell carcinoma (non-melanoma skin [91,92,93,94,95], and head and neck [96,97,98,99]), as well as non-small cell lung cancer [100,101,102,103]. Additionally high expression of GNB2 is associated with an aggressive form of pulmonary adenocarcinoma (mixed adenocarcinoma with bronchioalveolar features), and shorter overall survival for patients with these tumors [104].…”

Angiogenic and signalling proteins correlate with sensitivity to sequential treatment in renal cell cancer

“…All the three agents resulted to be active in inhibiting cell proliferation, with a major effect observed after everolimus treatment (Figure 2A). In fact, even if both TKIs sunitinib and sorafenib were moderately effective in inhibiting proliferation of RCC cells in vitro at doses comparable to those used in our study (Juengel et al , 2009; Liu et al , 2009; Takeuchi et al , 2010; Huang et al , 2011; Kim et al , 2012), the target of everolimus, mTOR, is directly implicated in tumour cell proliferation and survival via PI3K, Akt and MAPK. The doses of drugs chosen by us and in similar studies are expected to be in the therapeutic range achieved in human studies.…”

Protein kinase C and cancer: what we know and what we do not

“…Enhanced PKCε levels are associated with invasion and/or metastasis of human breast, glioma and renal cell carcinoma [7, 166, 181]. PKCε contains an actin-binding motif that positions this kinase within a cytoskeletal matrix where many PKC substrates are localized [182–185].…”