bcl-2 over-expression enhances NF-?B activity and induces mmp-9 transcription in human MCF7ADR breast-cancer cells

Ricca, Alfredo; Biroccio, Annamaria; Bufalo, Donatella Del; Mackay, Andrew R.; Santoni, Angela; Cippitelli, Marco

doi:10.1002/(sici)1097-0215(20000415)86:2<188::aid-ijc7>3.0.co;2-w

Cited by 91 publications

(52 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The elements controlling the expression of MMP-9 have been well characterized and include AP-1, NF-kB, Ets and Sp1 sites, mainly within À670 bp region upstream to the transcription start site (Sato and Seiki, 1993). In particular, both the AP-1 and NF-kB binding sites have been shown to be important regulatory elements of the MMP-9 promoter (Ricca et al, 2000;Troussard et al, 2000). Serum-induced activation of ERK5 results in the transcriptional activation of c-jun by the MEF2C transcription factor (Kato et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion

et al. 2003

View full text Add to dashboard Cite

The novel mitogen/extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ ERK5) pathway has been implicated in the regulation of cellular proliferation. MEK5 expression has been detected in prostate cancer cells, although the significance of the MEK5/ERK5 pathway in human prostate cancer has not been tested. We examined MEK5 expression in 127 cases of prostate cancer and 20 cases of benign prostatic hypertrophy (BPH) by immunohistochemistry and compared the results to clinical parameters. We demonstrated that MEK5 expression is increased in prostate cancer as compared to benign prostatic tissue. Strong MEK5 expression correlates with the presence of bony metastases and less favourable disease-specific survival. Furthermore, among the patients with high Gleason score of 8-10, MEK5 overexpression has an additional prognostic value in survival. MEK5 transfection experiments confirm its ability to induce proliferation (Po0.0001), motility (P ¼ 0.0001) and invasion in prostate cancer cells (P ¼ 0.0001). MEK5 expression drastically increased MMP-9, but not MMP-2 mRNA expression. Luciferase report assays suggest that the À670/MMP-9 promoter is upregulated by MEK5 and electromobility shift assay further suggests the involvement of activator protein-I (AP-1), but not the NF-jB, binding site in the MMP-9 promoter. Using an AP-1 luciferase construct, activation of MEK5 was confirmed to enhance AP-1 activities up to twofold. Taken together, our results establish MEK5 as a key signalling molecule associated with prostate carcinogenesis. As the MEK5/ERK5 interaction is highly specific, it represents a potential target of therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion

et al. 2003

View full text Add to dashboard Cite

show abstract

“…It is therefore tempting to speculate that in melanoma cells Bcl-2 might activate SphK via VEGF upregulation. In addition, the transcription factor NF-kB has been linked to Bcl-2 expression in MCF7 ADR cells (Ricca et al, 2000). NF-kB regulates the expression of numerous genes important for cell survival, tumor progression and invasion (Bours et al, 2000), and constitutive NF-kB activity has been associated with tumor development and progression (Yamamoto and Gaynor, 2001).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression

et al. 2005

View full text Add to dashboard Cite

While most of the pharmacological therapies for melanoma utilize the apoptotic machinery of the cells, the available therapeutic options are limited due to the ability of melanoma cells to resist programmed cell death. Human melanoma cell lines A-375 and M186 are sensitive to ceramide-and Fas-induced cell death, while Mel-2a and M221 are resistant. We have now found that Mel-2a and M221 cells have a significantly higher ceramide/sphingosine-1-phosphate (S1P) ratio than A-375 and M186 cells. As sphingosine kinase (SphK) type 1 plays a critical role in determining the dynamic balance between the proapoptotic sphingolipid metabolite ceramide and the prosurvival S1P, we examined its role in apoptosis of melanoma cells. Increasing SphK1 expression reduced the sensitivity of A-375 melanoma cells to Fas-and ceramide-mediated apoptosis. Conversely, downregulation of SphK1 with small interfering RNA decreased the resistance of Mel-2a cells to apoptosis. Importantly, overexpression of the prosurvival protein Bcl-2 in A-375 cells markedly stimulated SphK1 expression and activity, while downregulation of Bcl-2 reduced SphK1 expression. This link between Bcl-2 and SphK1 might be an additional clue to chemotherapy resistance of malignant melanoma.

show abstract

“…Over-expression of Bcl-2 in myocytes, breast cancer cells, and photoreceptor cells results in lower levels of IkBa and increased NF-kB activity (Crawford et al, 2001;de Moissac et al, 1998de Moissac et al, , 1999Ricca et al, 2000). Although the mechanism of IkBa repression by Bcl-2 is not clear, studies indicate that this repression requires the Bcl-2 BH4 domain and is related to the phosphorylation and degradation of IkBa (de Moissac et al, 1999;Ricca et al, 2000). These studies, together with our results, suggest a potential feedback pathway where NF-kB increases Bcl-2 expression, which in turn inhibits IkBa, further enhancing NF-kB activity.…”

Section: Discussionmentioning

confidence: 99%

NF-κB activates Bcl-2 expression in t(14;18) lymphoma cells

2002

View full text Add to dashboard Cite

The t(14;18) translocation, which is characteristic of follicular lymphoma, results in the overexpression of the bcl-2 gene dependent upon regulatory elements within the bcl-2 5' flanking region and the immunoglobulin heavy chain gene enhancers. Con¯icting evidence exists on the e ects of NF-kB expression on Bcl-2 levels in di erent cell types. Lymphoma cells with the t(14;18) translocation show high levels of nuclear NF-kB proteins. We observed decreased levels of endogenous Bcl-2 when the IkBa-super-repressor was expressed in a t(14;18) cell line. Deletion analysis of the bcl-2 promoter indicated that the repressive e ect of the IkBa-super-repressor occurred through a region that contained no NF-kB consensus sequences. This highly active region contained a c-AMP response element (CRE) and several Sp1 binding sites. Chromatin immunoprecipitation assays with antibodies speci®c for the NF-kB and CREB/ATF family members, as well as Sp1, resulted in the isolation of this IkBa-super-repressor responsive region of the bcl-2 promoter. Mutation of the CRE and the two Sp1 sites in di erent combinations in bcl-2 reporter constructs resulted in the loss of bcl-2 promoter repression by the IkBa-super-repressor. We therefore conclude that the activation of bcl-2 by NF-kB in t(14;18) lymphoma cells is mediated through the CRE and Sp1 binding sites.

show abstract

bcl-2 over-expression enhances NF-?B activity and induces mmp-9 transcription in human MCF7ADR breast-cancer cells

Cited by 91 publications

References 21 publications

MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion

MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion

Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression

NF-κB activates Bcl-2 expression in t(14;18) lymphoma cells

Contact Info

Product

Resources

About