CD95-Mediated Apoptosis Is Impaired at Receptor Level by Cellular FLICE-Inhibitory Protein (Long Form) in Wild-Type p53 Human Ovarian Carcinoma

Mezzanzanica, Delia; Balladore, Emanuela; Turatti, Fabio; Luison, Elena; Alberti, Paola; Bagnoli, Marina; Figini, Mariangela; Mazzoni, Alessandra; Raspagliesi, Francesco; Oggionni, Maria; Pilotti, Silvana; Canevari, Silvana

doi:10.1158/1078-0432.ccr-03-0537

Cited by 50 publications

(44 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, c-FLIP L expression was higher in p53 wild-type tumors than in p53-mutated tumors (Table 3). A similar result was also reported for ovarian carcinoma, indicating that c-FLIP L overexpression was more common in p53 wild-type tumors than in p53-mutated tumors (31). The positive correlation between FasL and c-FLIP L in lung tumors and their prognostic significance were also observed in colorectal and bladder urothelial carcinomas (23,43).…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

A Polymorphic −844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

Sung

Wang

Cheng

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Fas ligand (FasL) À844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL À844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL À844T/C polymorphism on the clinical outcome of non-small cell lung cancer (NSCLC) remains to be identified.Experimental Design: A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL À844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL À844T/C polymorphism on survival and relapse was determined by Kaplan-Meier analysis and Cox proportional hazards models.Results: The FasL À844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P ¼ 0.008). In addition, patients with the FasL À844CC genotype were more prone to tumor relapse than those with the FasL À844TTþTC genotype (62.1% vs. 37.9%, P ¼ 0.001). Multivariate Cox regression analysis showed that patients with the FasL À844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL À844TTþTC genotype (24

show abstract

Section: Discussionsupporting

confidence: 79%

“…Anti-FasL (1/500) polyclonal primary antibody (N-20; Santa Cruz Biotechnology) and anti-c-FLIP L (1/100) polyclonal primary antibody (C-19; Santa Cruz Biotechnology) were used (26,31). An immunohistochemistry detection kit for in vitro diagnostic use (Invitrogen) was used according to the standard protocol.…”

Section: Translational Relevancementioning

confidence: 99%

A Polymorphic −844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

Sung

Wang

Cheng

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…An association between c-FLIP expression and resistance to apoptosis mediated by CD95 as well as by TRAIL has been reported for several cancer types (Abedini et al 2004, Rippo et al 2004, Horak et al 2005, Longley et al 2006, Rogers et al 2007, and c-FLIP expression was already reported to be an unfavorable prognostic indicator in some oncotypes other than ovarian carcinoma (Chen et al 2005, Valnet-Rabier et al 2005, Ullenhag et al 2007). In EOC cell lines, we have recently identified the long isoform of c-FLIP (c-FLIP L ) as one of the molecules directly involved in the impairment of apoptotic signaling in the context of functional p53; in the same study, we also found an inverse relationship between c-FLIP L overexpression and p53 nuclear accumulation in a small number of EOC specimens (Mezzanzanica et al 2004). Additionally, Tsang's group reported the involvement of c-FLIP L in regulating EOC cisplatin sensitivity in concert with p53 and the ubiquitin ligase Itch (Abedini et al 2004(Abedini et al , 2008, further suggesting a role for c-FLIP L as a survival factor in EOC cell lines.…”

Section: Introductionmentioning

confidence: 54%

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

Bagnoli¹,

Ambrogi²,

Pilotti³

et al. 2009

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIP L ) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIP L downmodulation. Here, we studied the association between c-FLIP L and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIP L and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical-pathological characteristics and biological determinants. IHC revealed c-FLIP L expression and p53 nuclear accumulation inversely related (PZ0.0001; odds ratioZ0.29, confidence interval (CI)Z0.15-0.055). MCA indicated that p53 accumulation was associated to clinical-pathological variables, while c-FLIP L expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan-Meier curves showed a reduced survival time according to c-FLIP L expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P valueZ0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIP L expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratioZ1.82, 95% CIZ1.17-2.82; PZ0.008). Altogether these data support the independent contribution of c-FLIP L in refining the prognostic information obtained from standard clinical-pathological indicators, confirming its pivotal role in promoting cell survival.

show abstract

“…15 Briefly, tissue lysates were obtained from ovarian tumor specimens collected as cryostatic sections (10/ specimen, 5 lm each), directly solubilized with loading buffer and boiled for 5 min at 95°C. Lysates (40 lg in the case of cell lines and half of the sample in the case of tumor specimens) were separated by 10% SDS-PAGE and transferred to a nitrocellulose membrane (Hybond C-Super, Amersham).…”

Section: Western Blotting Analysis Of M-cam Expressionmentioning

confidence: 99%

M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

Aldovini

Demichelis²,

Doglioni³

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Currently available clinico–pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M‐CAM) in EOC. Using the same antibody, M‐CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan–Meier method and Cox proportional hazards analysis were used to relate M‐CAM expression to clinico–pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M‐CAM expression from normal to malignant cells. M‐CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M‐CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log‐rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log‐rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front‐line treatment, M‐CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79–15.41 and p = 0.011, HR 3.77, 95% Cl 1.36–10.49 respectively) at the multivariate level. In the same sub‐group of patients, M‐CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42–6.88). M‐CAM is a marker of early relapse and poorer outcome in EOC. In particular, M‐CAM expression identifies a subgroup of front‐line therapy‐responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities. © 2006 Wiley‐Liss, Inc.

show abstract

CD95-Mediated Apoptosis Is Impaired at Receptor Level by Cellular FLICE-Inhibitory Protein (Long Form) in Wild-Type p53 Human Ovarian Carcinoma

Cited by 50 publications

References 35 publications

A Polymorphic −844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

A Polymorphic −844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

Contact Info

Product

Resources

About