Proliferating Cell Nuclear Antigen, Survivin, and CD34 Expressions in Pancreatic Cancer and Their Correlation With Hypoxia-Inducible Factor 1α

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Abstract
Hypoxia-inducible factor 1alpha (HIF-1alpha) has been universally detected in many types of cells and plays a key role in modulation of tumor-related genes. The purpose of this study was to explore the relationship between HIF-1alpha messenger RNA (mRNA) expression and biologic characteristics in pancreatic cancer, such as tumor angiogenesis, tumor cell proliferation, differentiation, apoptosis, and metastasis. Reverse transcriptase-polymerase chain reaction was used to detect HIF-1alpha mRNA expression. The expressions of survivin, proliferating cell nuclear antigen (PCNA), and CD34 proteins were measured immunohistochemically. The correlation between the expression levels of HIF-1alpha mRNA and survivin, PCNA, and CD34 were analyzed. There was very significant difference in the expression of HIF-1alpha between the pancreatic cancer tissue and adjacent normal tissue (P < 0.01), but no significant difference was found among tumor histopathologic grades (P > 0.05). There was significant difference in the expression of HIF-1alpha mRNA between Japanese Pancreatic Society stages I to II and stages III to IV (P < 0.05). The expression of HIF-1alpha mRNA was closely correlated with the expression of survivin, PCNA, and CD34 proteins. The expression level of HIF-1alpha mRNA is surmised to have a significant correlation with tumor angiogenesis, cell proliferation, apoptosis, and metastasis. Inhibition of HIF-1alpha may be an important and approachable therapeutic target for pancreatic cancer.