Sp1 regulates osteopontin expression in SW480 human colon adenocarcinoma cells

Takami, Yoji; Russell, M Benjamin; Gao, Chengjiang; Mi, Zhiyong; Guo, Hongtao; Mantyh, Christopher R.; Kuo, Paul C.

doi:10.1016/j.surg.2007.02.015

Cited by 30 publications

(32 citation statements)

References 18 publications

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“…Consistent with that prediction, OPN promoterluciferase reporter construct demonstrated significantly higher activity in the LSF-17 clone compared to the Control-8 clone (Fig. 6E) (16). Finally, a chromatin immunoprecipitation (ChIP) assay confirmed LSF binding to the OPN promoter (Fig.…”

Section: Resultssupporting

confidence: 83%

“…For the NF-κB luciferase reporter assay, cells were plated into 24-well plates and the next day transfected with 3κB-luc (luciferase reporter plasmid containing three tandem repeats of NF-κB binding site) and renilla luciferase expression plasmid for transfection control (21). Cells were incubated in the absence or presence of TNF-α (10 ng/mL) for 12 h. For the OPN promoter luciferase assay, cells were transfected with OPN-Prom-Luc construct containing ∼1 kb of OPN promoter upstream of the luciferase gene (kindly provided by Paul C. Kuo, Duke University) along with a renilla luciferase expression plasmid (16). Luciferase assays were measured using a Dual Luciferase Reporter Assay kit (Promega) according to the manufacturer's protocol, and firefly luciferase activity was normalized by renilla luciferase activity.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Transcription factor Late SV40 Factor (LSF) functions as an oncogene in hepatocellular carcinoma

Yoo¹,

Emdad

Gredler³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

106

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Hepatocellular carcinoma (HCC) is a highly aggressive cancer with no currently available effective treatment. Understanding of the molecular mechanism of HCC development and progression is imperative for developing novel, effective, and targeted therapies for this lethal disease. In this article, we document that the cellular transcription factor Late SV40 Factor (LSF) plays an important role in HCC pathogenesis. LSF protein was significantly overexpressed in human HCC cells compared to normal hepatocytes. In 109 HCC patients, LSF protein was overexpressed in >90% cases, compared to normal liver, and LSF expression level showed significant correlation with the stages and grades of the disease. Forced overexpression of LSF in less aggressive HCC cells resulted in highly aggressive, angiogenic, and multiorgan metastatic tumors in nude mice. Conversely, inhibition of LSF significantly abrogated growth and metastasis of highly aggressive HCC cells in nude mice. Microarray studies revealed that as a transcription factor, LSF modulated specific genes regulating invasion, angiogenesis, chemoresistance, and senescence. The expression of osteopontin (OPN), a gene regulating every step in tumor progression and metastasis, was robustly up-regulated by LSF. It was documented that LSF transcriptionally up-regulates OPN, and loss-of-function studies demonstrated that OPN plays an important role in mediating the oncogenic functions of LSF. Together, these data establish a regulatory role of LSF in cancer, particularly HCC pathogenesis, and validate LSF as a viable target for therapeutic intervention.metastasis | osteopontin | transcription regulation H epatocellular carcinoma (HCC) is one of the five most common cancers worldwide (1). The incidence of HCC is increasing despite a decrease in overall incidence of all cancers (2, 3). In the United States, the estimated new cases of HCC for 2008 were 21,370, of which 18,410 were expected to die (2). The mortality rate of HCC parallels that of its incidence because HCC is a tumor with rapid growth and early vascular invasion that is resistant to conventional chemotherapy, and no systemic therapy is available for the advanced disease (4). As such, understanding the molecular mechanism of HCC development and progression is imperative to establish novel, effective, and targeted therapies for this highly aggressive cancer. Our recent studies reveal that astrocyte elevated gene-1 (AEG-1) is overexpressed in >90% of human HCC patients, compared to normal liver, and AEG-1 plays a key role in regulating development and progression of HCC (5). The transcription factor Late SV40 Factor (LSF) was identified as a downstream gene of AEG-1, and we demonstrated that LSF mediates, in part, AEG-1-induced resistance to 5-fluorouracil (5-FU) in HCC cells (5, 6).LSF, also known as LBP-1c and TFCP2, regulates diverse cellular and viral promoters (7,8). A major cellular target of LSF is the thymidylate synthase (TS) gene, which encodes the ratelimiting enzyme in the production of dTTP, required for DNA ...

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Section: Resultssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Transcription factor Late SV40 Factor (LSF) functions as an oncogene in hepatocellular carcinoma

Yoo¹,

Emdad

Gredler³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Our study, for the first time, has described the expression of Sp1 in patients with pancreatic adenocarcinoma and showed the association of Sp1 with advanced stage and poor survival. Although there are many Sp1 site -dependent target proteins, it may be of interest to note that Sp1 has recently been shown to regulate osteopontin expression, a molecule that mediates cancer metastasis, in cells derived from colon adenocarcinoma (24), and our results in this study clearly showed that every pancreatic adenocarcinoma with Sp1 overexpression had lymph node metastasis. Additionally, Sp1 has also been shown to mediate p53-associated cellular actions (25), and p53 is one the most frequently mutated genes in pancreatic adenocarcinoma (26).…”

Section: Discussionsupporting

confidence: 53%

Sp1, a New Biomarker That Identifies a Subset of Aggressive Pancreatic Ductal Adenocarcinoma

Jiang

Woda²,

Banner³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

138

115

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Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Sp1 is a sequence-specific DNA binding protein that is important in the transcription of a number of regulatory genes involved in cancer cell growth, differentiation, and metastasis. In this study, we investigated Sp1 expression in pancreatic ductal adenocarcinoma and its association with clinical outcome. We studied 42 patients with primary pancreatic adenocarcinoma. The expression of Sp1 in pancreatic adenocarcinoma was evaluated by immunohistochemical staining. All 42 patients had clinical follow-up information and were evaluated for survival. Sp1 protein was aberrantly overexpressed in a subset of primary pancreatic adenocarcinoma. These tumors all developed metastasis, whereas none of the primary tumors without lymph node metastasis showed Sp1 overexpression. Statistically, Sp1 overexpression was associated with higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.036, and P < 0.0001, respectively). Additionally, patients of this subset had a much shorter overall survival than patients without Sp1 overexpression, as evidenced by Kaplan-Meier plots and the log-rank test (P = 0.002). The 5-year overall survival rate was 19% in patients with Sp1 overexpression, compared with 55% in patients without Sp1 overexpression. The median survival was only 13 months for patients with Sp1 overexpression, compared with 65 months for patients without Sp1 overexpression. In conclusion, Sp1 is a new biomarker that identifies a subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior. It can be used at initial diagnosis of pancreatic adenocarcinoma to identify patients with an increased probability of cancer metastasis and much shortened overall survival.

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“…It has been reported that Sp1 is involved in the development and progression of several types of cancers, including colorectal cancer (Dong et al, 2009). At present, CCND1, PDEGF, p21, VEGF, TGFβ, E2F1, c-fos, OPN, and TGFα are the cancer-related Sp1 targets that have been identified (Gartel et al, 2000;Zhu et al, 2002;Takami et al, 2007;Dong et al, 2009). There has been one study on the association of PPARD gene variants with upper aero-digestive tract cancers in patients from Los Angeles, CA, USA (Yang et al, 2014) and another on their association with colorectal cancer in patients from Switzerland (Ticha et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer

Rosales-Reynoso

et al. 2017

Genet. Mol. Res.

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ABSTRACT. PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-nodemetastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance.In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

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Sp1 regulates osteopontin expression in SW480 human colon adenocarcinoma cells

Abstract: Introduction-Osteopontin (OPN) mediates cancer metastatis. Mechanisms regulating OPN expression in human colorectal cancer are unknown. Using SW480 colon adenocarcinoma cells, we hypothesized that transcription determines OPN expression.

Cited by 30 publications

References 18 publications

Transcription factor Late SV40 Factor (LSF) functions as an oncogene in hepatocellular carcinoma

Transcription factor Late SV40 Factor (LSF) functions as an oncogene in hepatocellular carcinoma

Sp1, a New Biomarker That Identifies a Subset of Aggressive Pancreatic Ductal Adenocarcinoma

Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer

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