Dataset Information

TGF-?1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.

ABSTRACT: BACKGROUND:Ninety percent of pancreatic cancer patients have less than 5-year overall survival and approximately 50% of cases were diagnosed with metastasis in the time of admission. Previous evidences have demonstrated the strong association between TGF-?1 variations and cancer susceptibility so far. METHODS:A total of 78 patients with pancreatic cancer and 94 healthy controls were enrolled in this case- control study between 2007 and 2012. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of TGF-?1 rs rs1800469 and rs1800471 were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:The mean age of cases and the control group were 64.50 ± 13.718 and 40.12 ± 16.001, respectively. For polymorphism -509 C>T, the frequency of TT genotype were 31 (33.0), CT, 47(50) and CC, 16 (17) in control and 19 (24.4), 45 (57.7) and 14 (17.9) in cases respectively. In position +915 G>C, the frequency of GG genotype was 84 (89.4) and GC, 10 (10.6) in control and 71 (91.0) and 7 (9) in cases, respectively. We did not observe any significant differences in the genotype and allele frequencies of the TGF-?1-509 C>T (rs1800469) and codon +915 G>C (rs1800471) between the two study groups (P>0.05). CONCLUSION:we found that TGF-?1 gene polymorphisms rs1800469 and rs1800471 might not play a role in pancreatic cancer susceptibility in Iranian population.

SUBMITTER: Behboudi Farahbakhsh F

PROVIDER: S-EPMC5346819 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TGF-β1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.

Behboudi Farahbakhsh Faegheh F Nazemalhosseini Mojarad Ehsan E Azimzadeh Pedram P Goudarzi Faezeh F Mohammad Alizadeh Amir Houshang AH Haghazali Mehrdad M Mahmoudi Lamoki Reza R Asadzadeh Aghdaei Hamid H

Gastroenterology and hepatology from bed to bench 20170101 1

<h4>Background</h4>Ninety percent of pancreatic cancer patients have less than 5-year overall survival and approximately 50% of cases were diagnosed with metastasis in the time of admission. Previous evidences have demonstrated the strong association between TGF-β1 variations and cancer susceptibility so far.<h4>Methods</h4>A total of 78 patients with pancreatic cancer and 94 healthy controls were enrolled in this case- control study between 2007 and 2012. Genomic DNA was isolated from periphera ...[more]

PMID: 28496942

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive human malignancy and intrinsically resistant to conventional therapies. YAP1, as a key downstream effector of the Hippo pathway, plays an important role in tumorigenesis including PDAC. Alternative mRNA splicing of YAP1 results in at least 8 protein isoforms, which are divided into two subgroups (YAP1-1 and YAP1-2) based on the presence of either a single or double WW domains. We investigated the functions and regulatory mechanisms of YAP1-1 and YAP1-2 in PDAC cells induced by TGF-β to undergo epithelial-to-mesenchymal transition (EMT). CRISPR-Cas9 and shRNA were used to silence YAP1 expression in pancreatic cancer cells. Re-constituted lentivirus mediated overexpression of each single YAP1 isoform was generated in the parental knockout L3.6 cells. EMT was induced by treatment with TGF-β, EGF and bFGF in parental and the constructed stable cell lines. Western blot and qPCR were used to detect the expression of EMT markers. Scratch wound healing and transwell assays were used to detect cell migration. The stability and subcellular localization of YAP1 proteins were determined by Western blot analysis, immunofluorescence, as well as ubiquitination assays. We showed that TGF-β, EGF and bFGF all significantly promoted EMT in PDAC cells, which was inhibited by knockdown of YAP1 expression. Interestingly, YAP1-1 stable cells exhibited a stronger migratory ability than YAP1-2 cells under normal culture condition. However, upon TGF-β treatment, L3.6-YAP1-2 cells exhibited a stronger migratory ability than L3.6-YAP1-1 cells. Mechanistically, TGF-β treatment preferentially stabilizes YAP1-2 and enhances its nuclear localization. Furthermore, TGF-β-induced EMT and YAP1-2 activity were both blocked by inhibition of AKT signaling. Our results showed that both YAP1-1 and YAP1-2 isoforms are important mediators in the EMT process of pancreatic cancer. However, YAP1-2 is more important in mediating TGF-β-induced EMT, which requires AKT signaling.

Dataset Information

TGF-?1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.

Publications

TGF-β1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets