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HepaCAM inhibits clear cell renal carcinoma 786-0 cell proliferation via blocking PKCε translocation from cytoplasm to plasma membrane

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Abstract

Hepatocyte cell adhesion molecule (HepaCAM) plays a crucial role in tumor progression and has been recognized as a novel tumor suppressor gene. The high protein expression level of protein kinase Cε (PKCε) has been discovered in many tumor types. In the present study, we determined HepaCAM and PKCε protein levels in human clear cell renal cell carcinoma (ccRCC) tissues and analyzed the correlation between them. We observed an inverse relationship in the expression of HepaCAM and PKCε in ccRCC and adjacent normal tissues. In ccRCC tissue, HepaCAM expression was undetectable while PKCε expression was high; the opposite was found in the adjacent normal tissue. Western blot analysis demonstrated that PKCε cytosolic protein levels increased while plasma membrane protein levels decreased without any change in total protein following infection of the ccRCC cell line 786-0 with adenovirus-GFP-HepaCAM (Ad-GFP-HepaCAM). Moreover, the application of Ad-GFP-HepaCAM combined with a PKCε-specific translocation inhibitor (εV1-2) effectively inhibited 786-0 cell growth. Ad-mediated expression of HepaCAM in 786-0 cells reduced the levels of phosphorylated AKT and cyclin D1 and inhibited cell proliferation. In summary, our studies point to interesting connections between HepaCAM and PKCε in tissues and in vitro. HepaCAM may prevent the translocation of PKCε from cytosolic to particulate fractions, resulting in the inhibition of 786-0 cell proliferation. Therapeutic manipulation of these novel protein targets may provide new ways of treating ccRCC.

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Acknowledgments

The study was done in the Department of Laboratory Diagnosis, Chongqing Medical University.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Bing Tan, Zhen Quan, Xiangdong Xu, Xiaoliang Jiang & Xiaohou Wu

  2. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Jinxiang Tan

  3. Department of Laboratory Diagnosis, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Hongfei Du & Chunli Luo

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  1. Bing Tan
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  2. Jinxiang Tan
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  4. Zhen Quan
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  5. Xiangdong Xu
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  8. Xiaohou Wu
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Correspondence to Xiaohou Wu.

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Tan, B., Tan, J., Du, H. et al. HepaCAM inhibits clear cell renal carcinoma 786-0 cell proliferation via blocking PKCε translocation from cytoplasm to plasma membrane. Mol Cell Biochem 391, 95–102 (2014). https://doi.org/10.1007/s11010-014-1991-9

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  • DOI: https://doi.org/10.1007/s11010-014-1991-9

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