Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma

  • Authors:
    • H. Huynh
    • P. T. Do
    • T. H. Nguyen
    • P. Chow
    • P. H. Tan
    • T. H. Quach
    • T. Van
    • K. C. Soo
    • E. Tran
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1839
  • Pages: 1839-1847
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Southeast Asia. Hyperphosphorylation of retinoblastoma (pRB) by cyclin/CDKs in G1/S transition is required for its inactivation and cell cycle progression. In the present study, we report that phosphorylation of pRB at Ser780 and Ser795 was detected in 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively. pRB protein was undetectable in 13% (6 of 46) of HCCs examined. Phosphorylated pRB was localized in the nuclei of hepatocarcinoma cells. Benign hepatocytes exhibited very weakly or no nuclear staining for phosphorylated pRB. Over-expression of E2F-1, cyclin D1, Cdk-2, Cdk-4 and cyclin A was found in 64% (30 of 46), 43% (26 of 46), 28% (11 of 46), 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively and this was correlated with elevation of ERK. Treatment of HepG2 cells with MEK1/2 inhibitor U0126 resulted in cell cycle arrest, downregulation of cyclin D1 and Cdk-2 expression and inhibition of pRB phosphorylation at Ser780 and Ser795. Ectopic expression of activated MEK1 in HepG2 cells increased cyclin D1 and Cdk-2 expression, phosphorylation of pRB at Ser780 and Ser795, and percentage of cells in S phase. Our data indicate that activated ERK plays an important role in cyclin D1 and Cdk-2 expression and phosphorylation of pRB at Ser780 and Ser795 in liver cancer cells.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Huynh H, Do PT, Nguyen TH, Chow P, Tan PH, Quach TH, Van T, Soo KC and Tran E: Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma. Int J Oncol 25: 1839-1847, 2004.
APA
Huynh, H., Do, P.T., Nguyen, T.H., Chow, P., Tan, P.H., Quach, T.H. ... Tran, E. (2004). Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma. International Journal of Oncology, 25, 1839-1847. https://doi.org/10.3892/ijo.25.6.1839
MLA
Huynh, H., Do, P. T., Nguyen, T. H., Chow, P., Tan, P. H., Quach, T. H., Van, T., Soo, K. C., Tran, E."Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma". International Journal of Oncology 25.6 (2004): 1839-1847.
Chicago
Huynh, H., Do, P. T., Nguyen, T. H., Chow, P., Tan, P. H., Quach, T. H., Van, T., Soo, K. C., Tran, E."Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma". International Journal of Oncology 25, no. 6 (2004): 1839-1847. https://doi.org/10.3892/ijo.25.6.1839