Abstract
Purpose
Although deletions or inactivating mutations of the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) are involved in the development of a variety of tumors including glioblastoma, melanoma, prostate cancer, breast cancer, endometrial cancers etc., the role of PTEN expression in human primary hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to investigate the involvement of PTEN mRNA and protein expression in HCC.
Methods
The level of PTEN mRNA expression in HCC specimens was analyzed by Northern blot. PTEN poly-clonal antibody was raised by immunizing New Zealand white rabbit with (His)6-tagged PTEN fusion protein and characterized by Western blot. The level of PTEN protein expression was determined by immunohistochemistry. The significance of PTEN in HCC was analyzed by comparing its expression level with the clinicopathological parameters of HCC patients.
Results
Four transcripts of PTEN mRNA at 5.5 kb, 4.4 kb, 2.4 kb, and 1.8 kb were detected in most para-carcinoma liver tissues, and the expression level of PTEN mRNA in carcinoma liver tissues was found to decrease significantly. The poly-clonal antibody raised against histidine-tagged fusion PTEN protein showed specific immuno-reactivity to PTEN protein. Using the specific poly-clonal antibody prepared and characterized by ourselves, we found that PTEN protein was significantly down-regulated in HCC tissues compared with paired para-carcinoma tissues. The protein expression of PTEN is negatively associated with the pathological grading and presence of cancer thrombus of HCC.
Conclusions
Down-regulation of PTEN expression may play an important role in the development of HCC and the level of PTEN expression may be a potential adjuvant parameter in forecasting the progression and prognosis of HCC patients.
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Acknowledgements
We are grateful to Dr. Carolyn Worby of the University of Michigan for generously providing full-length wild type PTEN cDNA, and to Prof. Axel Ullrich of Department of Molecular Biochemistry in the Max Planck Institute for his generous gift of MCF-7 cells.
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Supported by Chinese National Distinguished Young Scholar Awards (No.39825114), Chinese National Key Project of Basic Research (No.G1998051210 and No.01CB510205) and the Key Project of the Chinese National Natural Science Foundation (No. 30000159 and No.39830080).
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Wan, XW., Jiang, M., Cao, HF. et al. The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma. J Cancer Res Clin Oncol 129, 100–106 (2003). https://doi.org/10.1007/s00432-002-0410-x
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DOI: https://doi.org/10.1007/s00432-002-0410-x