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SKP2/P27Kip1 pathway is associated with Advanced Ovarian Cancer in Saudi Patients

  • Hafez, Mohamed M (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Alhoshani, Ali R (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Al-Hosaini, Khaled A (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Alsharari, Shakir D (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Al Rejaie, Salim S (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Sayed-Ahmed, Mohamed M (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh) ;
  • Al-Shabanah, Othman A (Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Riyadh)
  • Published : 2015.09.02

Abstract

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

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