Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism

  • Authors:
    • Teresa Gómez del Pulgar
    • Fátima Valdés-Mora
    • Eva Bandrés
    • Rosa Pérez-Palacios
    • Carolina Espina
    • Paloma Cejas
    • Miguel Angel García-Cabezas
    • Manuel Nistal
    • Enrique Casado
    • Manuel González-Barón
    • Jesús García-Foncillas
    • Juan Carlos Lacal
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.185
  • Pages: 185-193
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Abstract

Cdc42, a member of Rho GTPases family, is involved in the regulation of several cellular functions, such as rearrangement of actin cytoskeleton, membrane trafficking, cell-cycle progression, and transcriptional regulation. Aberrant expression or activity of Cdc42 has been reported in several tumours. Here, the specific role of Cdc42 in development and progression of colorectal cancer was analyzed through microarrays technology. A comparative analysis of Cdc42 overexpressing cells versus cells with decreased Cdc42 levels through siRNA revealed that Cdc42 overexpression down-regulated the potential tumour suppressor gene ID4. Results were validated by quantitative RT-PCR and the methylation status of the specific promoter, analyzed. Methylation-specific PCR and bisulfite sequencing PCR analysis revealed that Cdc42 induced the methylation of the CpG island of the ID4 promoter. Colorectal adenocarcinoma samples were compared with the corresponding adjacent normal tissue of the same patient in order to determine specific gene expression levels. The downregulation of ID4 by Cdc42 was also found of relevance in colorectal adenocarcinoma biopsies. Cdc42 was found to be overexpressed with high incidence (60%) in colorectal cancer samples, and this expression was associated with silencing of ID4 with statistical significance (p<0.05). Cdc42 may have a role in the development of colon cancer. Furthermore, inhibition of Cdc42 activity may have a direct impact in the management of colorectal cancer.

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July 2008
Volume 33 Issue 1

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

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Spandidos Publications style
Gómez del Pulgar T, Valdés-Mora F, Bandrés E, Pérez-Palacios R, Espina C, Cejas P, García-Cabezas MA, Nistal M, Casado E, González-Barón M, González-Barón M, et al: Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism. Int J Oncol 33: 185-193, 2008.
APA
Gómez del Pulgar, T., Valdés-Mora, F., Bandrés, E., Pérez-Palacios, R., Espina, C., Cejas, P. ... Lacal, J.C. (2008). Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism. International Journal of Oncology, 33, 185-193. https://doi.org/10.3892/ijo.33.1.185
MLA
Gómez del Pulgar, T., Valdés-Mora, F., Bandrés, E., Pérez-Palacios, R., Espina, C., Cejas, P., García-Cabezas, M. A., Nistal, M., Casado, E., González-Barón, M., García-Foncillas, J., Lacal, J. C."Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism". International Journal of Oncology 33.1 (2008): 185-193.
Chicago
Gómez del Pulgar, T., Valdés-Mora, F., Bandrés, E., Pérez-Palacios, R., Espina, C., Cejas, P., García-Cabezas, M. A., Nistal, M., Casado, E., González-Barón, M., García-Foncillas, J., Lacal, J. C."Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism". International Journal of Oncology 33, no. 1 (2008): 185-193. https://doi.org/10.3892/ijo.33.1.185