OBJECTIVE: In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS: Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS: TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P = 0.0032). TRF1 expression correlated with the patient's length of survival (P < 0.001) and performance status (P < 0.001) and proved to be an independent indicator of length of survival. CONCLUSION: Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors. PMID:15792519[PubMed - indexed for MEDLINE]
Expression of telomeric repeat binding factor-1 in astroglial bran tumors
D'AVELLA, DOMENICO;
2005
Abstract
OBJECTIVE: In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS: Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS: TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P = 0.0032). TRF1 expression correlated with the patient's length of survival (P < 0.001) and performance status (P < 0.001) and proved to be an independent indicator of length of survival. CONCLUSION: Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors. PMID:15792519[PubMed - indexed for MEDLINE]
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