scholarly journals Role of Peroxisome Proliferator-Activated Receptorβ/δand B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jeffrey D. Coleman ◽  
Jerry T. Thompson ◽  
Russell W. Smith ◽  
Bogdan Prokopczyk ◽  
John P. Vanden Heuvel
Keyword(s):  
Pancreatic Cancer ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Pancreatic Cancer Cells

PPARβ/δis a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor,BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis thatPPARβ/δis expressed in human pancreatic cancer cells and that its activation could regulateMMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression ofMMP-9andPPARβ/δ, and lower levels ofBCL-6mRNA.PPARβ/δactivation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors ofPPARβ/δ,BCL-6, andMMP-9, it was evident thatPPARβ/δwas responsible for the ligand-dependent effects whereasBCL-6dissociation upon GW501516 treatment was ultimately responsible for decreasingMMP-9expression and hence invasion activity. These results suggest thatPPARβ/δplays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release ofBCL-6and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.

Basement Membrane Proteins Play an Important Role in the Invasive Processes of Human Pancreatic Cancer Cells

2008 ◽  
Vol 144 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Hirozumi Sawai ◽  
Yuji Okada ◽  
Hitoshi Funahashi ◽  
Hiroki Takahashi ◽  
Yoichi Matsuo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Membrane Proteins ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Basement Membrane Proteins

scholarly journals LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Xian-Ping Cui ◽  
Chuan-Xi Wang ◽  
Zhi-Yi Wang ◽  
Jian Li ◽  
Ya-Wen Tan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Candidate Target ◽  
Direct Target

Abstract LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.

scholarly journals bax, but notbcl-2, influences the prognosis of human pancreatic cancer

Gut ◽  
1998 ◽  
Vol 43 (3) ◽  
pp. 414-421 ◽  
Author(s):  
H Friess ◽  
Z Lu ◽  
H U Graber ◽  
A Zimmermann ◽  
G Adler ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Northern Blot ◽  
In Situ Hybridisation ◽  
Biological Significance ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Pancreatic Cancer Cells

Background—bcl-2and bax belong to thebcl-2-related gene family, which marks a new class of genes that influence apoptosis. Thebcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis.Aims—To analyse the expression of bcl-2 andbax in pancreatic cancer and correlate the results with clinical parameters.Patients—Pancreatic cancer tissue samples were obtained from 28 female and 32 male patients (median age 63, range 43–79 years) having surgery for pancreatic cancer. Normal pancreatic tissues obtained from 18 previously healthy organ donors served as controls.Methods—The levels ofbcl-2 and baxmRNA expression were analysed by northern blot and the exact site of mRNA transcription was determined by in situ hybridisation. The presence of the corresponding proteins was determined by immunohistochemistry.Results—Northern blot analysis indicated that, in comparison with the normal pancreas,bcl-2 mRNA was overexpressed in 30% andbax mRNA in 61% of the pancreatic cancer samples. Concomitant overexpression ofbcl-2 and bax was present in 26% of the cancer samples. Pancreatic adenocarcinomas exhibited 3.7-fold and 5.4-fold increases (p<0.001) inbcl-2 and baxmRNA levels respectively. In situ hybridisation showed that bothbcl-2 and baxmRNA were expressed in the cancer cells. Immunohistochemical analysis showed positive Bcl-2 and Bax immunostaining in 28 and 83% of the cancer samples respectively. In multivariate analysis (Cox regression model), bax expression was found to be a strong indicator of survival (p<0.001). Patients whose tumours exhibited Bax immunostaining lived significantly longer (12 months) than those whose tumours were Bax negative (five months) (p<0.039). In contrast, no relation was found between Bcl-2 and survival time.Conclusions—The data indicate that genes that are involved in the regulation of apoptosis are upregulated in human pancreatic cancer cells. Prolonged survival times in patients in whom apoptosis promoting factors are upregulated indicate that apoptotic pathways are of biological significance in pancreatic cancer.

scholarly journals Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 639
Author(s):  
Concetta Panebianco ◽  
Nadia Trivieri ◽  
Annacandida Villani ◽  
Fulvia Terracciano ◽  
Tiziana Pia Latiano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Human Pancreatic Cancer ◽  
Cancer Drug ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Pancreatic Cancer Cells

Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. In the current study, we investigated the role of miR-217, which is strongly down-regulated in cancerous, compared to normal, pancreatic tissues or cells, in sensitizing human pancreatic cancer cell lines to this drug. The low expression of miR-217 in pancreatic cancer patients was confirmed in two gene expression datasets (GSE41372 and GSE60980), and the prognostic value of two target genes (ANLN and TRPS1), was estimated on clinical data from the Tumor Cancer Genome Atlas (TCGA). Transfecting miR-217 mimic in pancreatic cancer cells reduced viability, enhanced apoptosis, and affected cell cycle by promoting a S phase arrest in gemcitabine-treated cells. Moreover, in drug-exposed cells subjected to miR-217 forced expression, a down-regulation for several genes involved in cancer drug resistance was observed, many of which are cell cycle regulators, such as CCND1, CCNE1, CDK2, CDKN1A, CDKN1B, while others, such as ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4, and RARA are involved in proliferation and cell cycle progression. Our results support the notion that miR-217 enhances pancreatic cancer sensitivity to gemcitabine, mainly impairing cell cycle progression.

In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Antitumor Efficacy ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells
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