Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

Wang, Dongyan; Yamamoto, Shunsuke; Hijiya, Naoki; Benveniste, Etty N.; Gladson, Candece L.

doi:10.1038/sj.onc.1203917

Cited by 66 publications

(48 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first one, located at Ϫ106 on the rat OPN promoter, is associated with SMC differentiation (24) and glucose signaling (42) and is conserved in the mouse and human promoter, although its function has not been demonstrated in these species. A second Ebox, located at Ϫ81 in the mouse promoter (25) and at Ϫ84 in the human promoter (43), was also shown to be involved in glucose signaling (25). According to our data, none of these sites are involved in UTP-induced OPN expression.…”

Section: Discussionmentioning

confidence: 85%

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Renault

Jalvy

Potier

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Osteopontin (OPN) is an important chemokinetic agent for several cell types. Our earlier studies have shown that its expression is essential for uridine triphosphate (UTP)-mediated migration of vascular smooth muscle cells. We demonstrated previously that the activation of an AP-1 binding site located 76 bp upstream of the transcription start in the rat OPN promoter is involved in the induction of OPN expression. In this work, using a luciferase promoter deletion assay, we identified a new region of the rat OPN promoter (؊1837 to ؊1757) that is responsive to UTP. This region contains an NFB site located at ؊1800 and an Ebox located at ؊1768. Supershift electrophoretic mobility shift assay and chromatin immunoprecipitation assays identified NFB and USF-1/USF-2 as the DNA binding proteins induced by UTP, respectively, for these two sites. Using dominant negative mutants of IB kinase and USF transcription factors, we confirmed that NFB and USF-1/USF-2 are involved in the UTP-mediated expression of OPN. Using a pharmacological approach, we demonstrated that USF proteins are regulated by the extracellular signal-regulated kinase (ERK)1/2 pathway, just as the earlier discovered AP-1 complex, whereas NFB is up-regulated through PKC␦ signals. Finally, our work suggests that the UTPstimulated OPN expression involves a coordinate regulation of PKC␦-NFB, ERK1/2-USF, and ERK1/2/ NAD(P)H oxidase AP-1 signaling pathways. Osteopontin (OPN)1 is a multifunctional phosphoprotein secreted by many cell types such as osteoclasts, lymphocytes, macrophages, epithelial cells, and smooth muscle cells (SMCs).Its expression is induced during vessel remodeling, as well as wound healing and bone synthesis (1). Overexpression of OPN can be found in pathological settings, such as immunological disorders, neoplastic transformation, metastasis, and formation of urinary stones. Its role in cell migration has been established in vitro in various cell types, including osteoclasts (2), macrophages (3), endothelial cells (4), and SMCs (5, 6). In vivo studies have established that OPN contributes to SMC recruitment into atherosclerotic plaques (7) and neointimal thickening (8), to osteoclast recruitment during bone resorption, (2) and to macrophage recruitment at inflammatory sites (atherosclerotic plaque, granulomas) (3).In the context of vascular remodeling, soluble factors, such as angiotensin II, basic fibroblast growth factor, plateletderived growth factor, interleukin-1 (9), and the nucleotides ATP and UTP (10), all induce expression of OPN. Moreover, nucleotides also modulate contraction, proliferation, and migration of vascular SMCs (11). They act through G proteincoupled P2Y receptors (12) and activate phospholipase C, resulting in elevated levels of intracellular free Ca 2ϩ and activation of PKC. In addition, they induce ROS production through NAD(P)H oxidase (13). Several transcription factors, such as NFAT, AP-1, cAMP-responsive element-binding protein, serum-responsive factor, STAT, and NFB are induced in UTP-stimulated SMCs (14), contro...

show abstract

Section: Discussionmentioning

confidence: 85%

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Renault

Jalvy

Potier

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…2A and B, a series of factors were secreted and increased in CM* compared with the control medium. Many of these factors were associated with tumor cell malignant phenotype, including chemotherapy resistance and tumor progression, migration and invasion (27)(28)(29). CCL5 was significantly increased up to ~72-fold compared with the control medium.…”

Section: Ccl5 Is Strongly Secreted From Cafs After Cisplatin Treatmentmentioning

confidence: 94%

Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

Zhou

Sun

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Currently, acquired resistance to cisplatin (DDP) is a substantial obstacle to reducing the morbidity and mortality due to ovarian malignant tumors. Nevertheless, cisplatin plays a vital role in killing the tumor cells while it may also be a 'primer' involved in chemotherapy resistance. We found that the cisplatin-induced chemokine (C-C motif) ligand 5 (CCL5) secretion derived from cancer-associated fibroblasts (CAFs) promoted ovarian cancer cell resistance to cisplatin. Via a cytokine chip assay, we identified a spectrum of secreted proteins that were derived from the CAFs through cisplatin-induced treatment. Among these, CCL5 significantly attenuated the cytotoxic effect of cisplatin chemotherapy in vitro and in vivo. Additionally, CCL5 expression was also detected in 62 serous ovarian cancer patient tissue specimens using IHC, and the results demonstrated that chemotherapy resistant patients displayed higher expression of CCL5 than the chemo-sensitive patients (P<0.05). Mechanistically, we found that CCL5 notably increased STAT3 and Akt phosphorylation levels in ovarian cancer cells. These results indicated that cisplatininduced CCL5 secretion derived from the CAFs may promote cisplatin resistance, which was mediated by regulation of the STAT3 and PI3K/Akt signal pathways.

show abstract

“…The SNP at Ϫ66 was predicted to bind the SP1 transcription factor both by the knowledge that the sequence between Ϫ68 and Ϫ59 is an SP1 binding site in the human OPN promoter (39) and by promoter analysis with the MatInspector software. This was confirmed by our EMSA in which we showed that SP1 and SP3 factors recognize this site and that the allele with the T nucleotide inside the SP1 recognition sequence has a higher binding affinity.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the osteopontin promoter affect its transcriptional activity

Giacopelli

Marciano

Pistorio

et al. 2004

Physiological Genomics

120

133

View full text Add to dashboard Cite

.-Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at Ϫ66, Ϫ156, and Ϫ443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the Ϫ66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the Ϫ156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the Ϫ443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.

show abstract

Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions

Cited by 66 publications

References 34 publications

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

Polymorphisms in the osteopontin promoter affect its transcriptional activity

Contact Info

Product

Resources

About