Article ID Journal Published Year Pages File Type
3943160 Gynecologic Oncology 2015 5 Pages PDF
Abstract

•A significant down-regulation in the gene expression of TLRs 3, 4 and 5 was observed in cervical squamous cell cancer.•A significant up-regulation in the gene expression of TLR 1 was observed in cervical squamous cell cancer.•Study results evoke the proposition of investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.

ObjectiveHuman papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC).MethodsGene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting.ResultsHPV was detected in all cases and in none of the controls (p < 0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p < 0.0001), TLR4 (p < 0.0005) and TLR5 (p < 0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p = 0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies.ConclusionsA significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.

Related Topics
Health Sciences Medicine and Dentistry Obstetrics, Gynecology and Women's Health
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