Fas-mediated apoptosis in seven human prostate cancer cell lines: Correlation with tumor stage

Hedlund, Tammy E.; Duke, Richard C.; Schleicher, Mary S.; Miller, Gary J.

doi:10.1002/(sici)1097-0045(19980701)36:2<92::aid-pros4>3.0.co;2-g

Cited by 79 publications

(53 citation statements)

References 34 publications

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“…Based on our results, as well as those published previously, 34,61,62 we conclude that while the majority of BTs have a functional Fas and/or TRAIL apoptotic pathway, a certain fraction of them (between 25 and 35%) are resistant through a number of different apoptotic pathway alterations. [37][38][39][61][62][63][64] However, high caspase-8:c-FLIP ratio was not in itself indicative of high sensitivity to either FasL-GFP or to TRAIL. These observations are consistent with the general mechanism of receptor-ligand-mediated signal transduction, where multiple components have to interact to propagate the signal, and conversely the signal can be blocked or degraded by mutations or dysregulation of those components.…”

Section: Discussionmentioning

confidence: 99%

“…35,36 These vectors have not been uniformly successful against tumors established in animal models. 25,27,[37][38][39] Lack of efficacy has generally been blamed on the acquired resistance of many tumor isolates to FasL-or TRAIL-mediated apoptosis. However, problems with vector delivery, sufficiently high transgene expression levels and the stability of the expressed protein may also play a significant role.…”

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confidence: 99%

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Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Rubinchik

Woraratanadharm

et al. 2003

Cancer Gene Ther

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Brain tumors (BTs) are among the most malignant forms of human cancer. Unfortunately, current treatments are often ineffective and produce severe side effects. Cytotoxic gene therapy is an alternative treatment strategy, with the potential advantages of reduced toxicity to normal brain tissue. Apoptosis-inducing ''death ligands'' Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) are genes with substantial cytotoxic activity in susceptible tumor cells. Here, we compared the effectiveness of Ad vectormediated delivery of Fas ligand-green fluorescent protein (FasL-GFP) fusion protein, human TRAIL, and both genes simultaneously. We examined a panel of 13 cell lines (eight derived from primary isolates) for susceptibility to Ad5-based vector infection and for sensitivity to FasL-and TRAIL-mediated apoptosis. All cell lines were efficiently transduced, but, as expected, varied in their sensitivity to ligand-induced apoptosis. Generally, sensitivity to FasL-GFP correlated with cell surface FasR levels, but no such correlation was seen for TRAIL and its functional receptors, DR4 and DR5. The vector expressing both FasL-GFP and TRAIL was more effective than either of the single-gene vectors at comparable transduction levels, and it was effective against a broader range of cell lines. In five cell lines, coexpression resulted in apoptosis levels greater than those predicted for strictly additive activity of the two death ligands. We believe that Ad vector-mediated delivery of multiple death ligands may be developed as a potential BT therapy, either alone or in conjunction with surgical resection of the primary tumor.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Rubinchik

Woraratanadharm

et al. 2003

Cancer Gene Ther

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“…Malignant cells, both lymphoid and non-lymphoid, manifest resistance to Fasmediated apoptosis [140][141][142][143][144][145][146][147][148][149]. Inasmuch as inhibition of Fas signaling for cell death is associated with tumor development and progression, it appears that Fas-mediated apoptosis constitutes at least a portion of anti-tumor immunity, and that some malignancies take advantage of mechanisms that block Fas killing to maintain viability and co-exist within the framework of a normal immune system [100,101], [150][151][152][153].…”

Section: Summary and Discussionmentioning

confidence: 99%

Inducible resistance to Fas-mediated apoptosis in B cells

Rothstein

2000

Cell Res

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Apoptosis produced in B cells through Fas (APO-1, CD95) triggering is regulated by signals derived from other surface receptors: CD40 engagement produces upregulation of Fas expression and marked susceptibility to Fas-induced cell death, whereas antigen receptor engagement, or IL-4R engagement, inhibits Fas killing and in so doing induces a state of Fas-resistance, even in otherwise sensitive, CD40-stimulated targets. Surface immunoglobulin and IL-4R utilize at least partially distinct pathways to produce Fas-resistance that differentially depend on PKC and STAT6, respectively. Further, surface immunoglobulin signaling for inducible Fas-resistance bypasses Btk, requires NF-κB, and entails new macromolecular synthesis. Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products, Bcl-xL and FLIP, and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule). faim was identified by differential display and exists in two alter-

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“…197 Recently, it has been shown that Fas expression is highly variable among human prostate cancer cell lines, and that it does not correlate with the sensitivity of the cells to anti-Fasmediated apoptosis. 52,198 Therefore, although Fas expression is necessary, it is not suf®cient to mediate apoptosis through this pathway. 198 Hedlund et al 198 have shown that prostate cancer cell lines which were derived from primary sites were sensitive to Fas-mediated apoptosis, whereas prostate cancer cell lines which were derived from distant metastases were resistant.…”

Section: Medical Approaches In the Management Of Prostate Cancermentioning

confidence: 99%

“…52,198 Therefore, although Fas expression is necessary, it is not suf®cient to mediate apoptosis through this pathway. 198 Hedlund et al 198 have shown that prostate cancer cell lines which were derived from primary sites were sensitive to Fas-mediated apoptosis, whereas prostate cancer cell lines which were derived from distant metastases were resistant. These data are in accordance with the in vivo loss of apoptotic potential during the progression of prostate cancer, although it is still unclear if Fas signalling plays a direct role in this phenomenon.…”

Section: Medical Approaches In the Management Of Prostate Cancermentioning

confidence: 99%

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

Costa-Pereira

Cotter

1999

Prostate Cancer Prostatic Dis

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Despite the high incidence and mortality rate of prostate cancer, the molecular mechanisms underlying the progression of the disease remain to be fully elucidated. This paper reviews the current state of knowledge on prostatic carcinogenesis, focusing not only on the molecular genetics of prostate cancer, but also on the role of oncogenes, tumour suppressor genes, and growth factors. The remarkable ability of prostate cancer cells to survive androgen withdrawal and apoptosis are discussed, with particular emphasis on how apoptosis may be manipulated from a therapeutic viewpoint.

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Fas-mediated apoptosis in seven human prostate cancer cell lines: Correlation with tumor stage

Cited by 79 publications

References 34 publications

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Inducible resistance to Fas-mediated apoptosis in B cells

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

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