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Aberrant Methylation of Pyk2 Gene Promoter Influences its Expression in Gastric Cancer Cell

Issue: Vol.8, No.4 - October 2009

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Article Type: Manuscript

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  1. Dr Xin Wang
    Department of general surgery, Peking University First Hospital
  2. Gang Hu
  3. Jing Zhu
  4. Tao Wu
  5. Yi-Sheng Pan
  6. Yu-Cun Liu
  7. Yuan-Lian Wan

Objective: Proline-rich tyrosine kinase 2 Pyk2 has been recognized as potential tumor suppressors in the occurrence and development of tumors. Aberrant methylation of CpG islands was found to be connected to the loss of gene function in tumor cells. DNA Methylation-specific PCR and real-time PCR were done in order to evaluate Pyk2's role in gastric cancer.
Methods: Eight CCGG sites of Pyk2 (proline-rich tyrosine kinase 2) gene promoter in gastric cancer cells were detected by enzyme-cutting PCR. Besides, we detected aberrant methylation of Pyk2 gene promoter in 55 respected primary gastric cancer tissues compared to 55 corresponding nonmalignant gastric tissues by MSP (methylation specific-PCR). Moreover, we investigated the effects of DAC (5-aza-2-deoxycytidine) and TSA (trichomycin A) in the expression of Pyk2 in gastric cancer cell lines.
Results: Six sites methylated in gastric cancer cell lines and only one site methylated in normal gastric cell line (P<0.05). Pyk2 gene methylation was detected in 34.5% tumor samples, which exists in only 1.82% of normal samples (P<0.05). However, there is no significant correlation between the methylation status and clinic pathological characteristics (P>0.05). It was found that TSA could increase the Pyk2 expression slightly, while DAC can significantly increase the expression of Pyk2, and the combination of DAC and TSA can increase its expression most.
Conclusion: Methylation of Pky2 promoter is highly expressed in gastric cancer, and TSA together with DAC can increase the expression of Pyk2 in gastric cancer.

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