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Expression of TRAIL (TNF-related apoptosis-inducing ligand) receptors in cervical cancer
H. S. Ryu1, K. H. Chang, S. J. Chang
1Departments of Obstetrics and Gynecology and Pathology, Ajou University School of Medicine, Suwon, Korea.
Abstract:
Apoptosis is an intrinsic and fundamental biologic process that plays a critical role in the normal development of multicellular organisms and in the maintainance of tissue homeostasis. Some of the well known regulators of apoptosis are cytokines of the tumor necrosis factor (TNF) ligand family, such as Fas ligand (Fas L) and TNF, which induce apoptosis by activation of their corresponding receptors, Fas and TNFR-1. Recently, a new member of the TNF family known as TRAIL (TNF-related apoptosis-inducing ligand) was identified and shown to induce p53-independent apoptosis in a variety of tumor cell lines but not in normal cells. Four human receptors for TRAIL were also recently identified and designated TRAIL-R1, -R2, -R3, and -R4. The aim of this study is to examine whether TRAIL and TRAIL receptors (-R1, -R2, -R3) are expressed in uterine cervical cancer and whether it is correlated with apoptosis, TRAIL, and TRAIL receptors. The subjects were 20 patients who were diagnosed with cervical cancer. Western blotting was performed in nine cases and immunohistochemical staining for TRAIL and TRAIL receptors (-R1, -R2, -R3) and TUNEL method for detection of apoptosis was performed in 11 cases. There were proteins for TRAIL, TRAIL-R1, -R2, and -R3 in tissues from cervical cancer. All TRAIL receptors were expressed in both normal cervical epithelium and tumor cells, and TRAIL-R1 and -R2 were more strongly expressed in tumor cells than normal epithelium (P < 0.05). Apoptosis correlated with expression of TRAIL-R1 and -R2 (P < 0.05). This study suggests that TRAIL induces apoptosis in cervical cancer through its receptors.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors are present in cervical cancer tissues. TRAIL receptor-1 and -2 expression correlates with apoptosis, suggesting TRAIL
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Apoptosis is crucial for tissue homeostasis and organism development.
- Tumor necrosis factor (TNF) ligands, like FasL and TNF, regulate apoptosis via specific receptors.
- TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not normal cells, acting through its receptors.
Purpose of the Study:
- To investigate the expression of TRAIL and its receptors (TRAIL-R1, -R2, -R3) in uterine cervical cancer.
- To determine the correlation between TRAIL, TRAIL receptors, and apoptosis in cervical cancer tissues.
Main Methods:
- Western blotting was used to detect protein expression of TRAIL and its receptors in nine cervical cancer cases.
- Immunohistochemical staining for TRAIL and TRAIL receptors (-R1, -R2, -R3) was performed on 11 cases.
- The TUNEL method was employed to detect and quantify apoptosis in the cervical cancer tissues.
Main Results:
- Proteins for TRAIL, TRAIL-R1, TRAIL-R2, and TRAIL-R3 were detected in cervical cancer tissues.
- TRAIL receptors were expressed in both normal cervical epithelium and tumor cells.
- TRAIL-R1 and TRAIL-R2 showed significantly higher expression in tumor cells compared to normal epithelium (P < 0.05).
- Apoptosis levels were found to correlate positively with the expression of TRAIL-R1 and TRAIL-R2 (P < 0.05).
Conclusions:
- TRAIL and its receptors are expressed in uterine cervical cancer.
- TRAIL receptor-1 and -2 are upregulated in cervical cancer tissues.
- TRAIL-R1 and -R2 expression is associated with increased apoptosis in cervical cancer, suggesting a role in tumor cell death.
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