Anaplastic and Atypical Meningiomas Express High Levels of Fas and Undergo Apoptosis in Response to Fas Ligation

Weisberg, S. H.; Ashkenazi, Ely; Israel, Zvi; Attia, Moshe; Shoshan, Yigal; Umansky, Félix; Brodie, Chaya

doi:10.1016/s0002-9440(10)62504-7

Cited by 8 publications

(8 citation statements)

References 29 publications

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“…Despite the importance of apoptosis in the development of central and peripheral nervous system, there are rather few reports concerning the magnitude of cell deletion in meningiomas [4][5][6][7].…”

Section: Discussionmentioning

confidence: 99%

“…In meningiomas, this relation may suggest a role of caspase-3 in the progression from benign to atypical tumors. Alternatively, caspase-3 upregulation as a marker of increased apoptosis may reflect increasing anaplasia and cell proliferation associated with increasing grade [7]. In this context, it is also possible that genes that are activated in higher grade lesions may also be responsible for the induction of a higher extent of apoptosis in them, as is the case of caspase recruitment by Fas activation shown to be upregulated in atypical and malignant meningiomas [7].…”

Section: Association Between Caspase-3 Expression and Histological Gradementioning

confidence: 99%

“…Alternatively, caspase-3 upregulation as a marker of increased apoptosis may reflect increasing anaplasia and cell proliferation associated with increasing grade [7]. In this context, it is also possible that genes that are activated in higher grade lesions may also be responsible for the induction of a higher extent of apoptosis in them, as is the case of caspase recruitment by Fas activation shown to be upregulated in atypical and malignant meningiomas [7]. Our finding of increasing apoptosis by means of caspase-3 expression in higher grade meningiomas is in accordance with the results of Ng and Chen [4] reporting increasing apoptotic rate by means of in-situ end-labeling of DNA fragments, along with the histological grade of these tumors.…”

Section: Association Between Caspase-3 Expression and Histological Gradementioning

confidence: 99%

“…Although the classical form of necrosis is a major histological factor influencing grading and prognosis in meningiomas [1][2][3], the occurrence and significance of apoptosis has been the subject of limited reports [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas

et al. 2006

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Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Association Between Caspase-3 Expression and Histological Gradementioning

confidence: 99%

Section: Association Between Caspase-3 Expression and Histological Gradementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas

et al. 2006

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“…They were cytologically characterized and described before (Weisberg et al, 2001). Glioblastomas were characterized and obtained from the Rabin Medical Center, Petach-Tikva, Israel.…”

Section: Cell Lines and Tissue Samplesmentioning

confidence: 99%

TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3

et al. 2004

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TMF/ARA160 is a Golgi resident protein whose cellular functions have not been conclusively revealed. Herein we show that TMF/ARA160 can direct the proteasomal degradation of the key cell growth regulator -Stat3. TMF/ARA160 was dispersed in the cytoplasm of myogenic C2C12 cells that were grown under low-serum conditions. The cytoplasmic distribution of TMF/ARA160 was accompanied by its transient association with the tyrosine kinase Fer and with Stat3, which underwent proteasomal degradation under those conditions. Moreover, serum deprivation induced the association of ubiquitinated proteins, with the TMF/ARA160 complex. However, TMF/ ARA160 did not bind Stat1, whose cellular levels were increased in serum-starved C2C12 cells. Amino-acid sequence analysis identified a BC-box element in TMF/ ARA160 that mediated the binding of this protein to elongin C. Ectopic expression of TMF/ARA160 in serumstarved C2C12 cells drove the ubiquitination and proteasomal degradation of Stat3, an effect that was not caused by TMF/ARA160 devoid of the BC-box motif. Thus, the Golgi apparatus harbors a novel BC-box-containing protein that can direct Stat3 to proteasomal degradation. Interestingly, the level of TMF/ARA160 was significantly decreased in malignant brain tumors, implying a suppressive role of that protein in tumor progression.

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Meningioma

The Genetics and Molecular Biology of Neural Tumors

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Anaplastic and Atypical Meningiomas Express High Levels of Fas and Undergo Apoptosis in Response to Fas Ligation

Abstract: In this study we characterized the expression of Fas and Fas ligand in different types

Cited by 8 publications

References 29 publications

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas

TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3

Meningioma

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