Glucose-Regulated Protein 78 (GRP78) Silencing Enhances Cell Migration but Does Not Influence Cell Proliferation in Hepatocellular Carcinoma
- 277 Downloads
GRP78 plays an essential role in embryonic development and in the therapeutic treatment and progression of cancer. However, little is known about the role of GRP78 in hepatocellular carcinoma (HCC).
In this study, we characterized five different HCC cell lines to examine GRP78 expression patterns and found that only HepJ5 cells ectopically overexpress GRP78. We knocked down GRP78 expression in HepJ5 cells using a small interfering RNA (siRNA), and the proliferation assay and migration assay were performed.
Using siRNA technique, we could successfully reduce GRP78 expression levels in HepJ5 cells. In a cell growth study, we found that GRP78-siRNA caused no significant changes in cellular proliferation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell cycle distribution. In a cell migration study, we found that GRP78-siRNA HepJ5 cells had dramatically increased migration ability in Transwell assay.
We conclude that ectopically expressed GRP78 does not contribute to the increased proliferation of HepJ5 cells, but does correlate with the migration of HCC cells under normoxic conditions.
KeywordsCell Cycle Distribution Ethylene Glycol Tetraacetic Acid Ethylene Glycol Tetraacetic Acid Ethylene Glycol Tetraacetic Acid GRP78 Expression
This work was supported by a grant from Taipei Medical University/Chi-Mei Medical Grant (96CM-TMU-06).
- 18.Chiou JF, Tai CJ, Huang MT, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2009 Oct 15 [Epub ahead of print] PMID: 19830497.Google Scholar
- 25.Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann Surg. 1990;211(3):277–87.Google Scholar
- 31.A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28(3):751–5.Google Scholar
- 32.Hsu C, Shen YC, Cheng CC, et al. Geographic difference in survival outcome for advanced hepatocellular carcinoma: Implications on future clinical trial design. Contemp Clin Trials. 2009 Sep 6 [Epub ahead of print].Google Scholar
- 41.Seitz SJ, Schleithoff ES, Koch A, et al. Chemotherapy-induced apoptosis in hepatocellular carcinoma involves the p53 family and is mediated via the extrinsic and the intrinsic pathway. Int J Cancer. 2009 Aug 26 [Epub ahead of print].Google Scholar