Mutations of theSmad2 andSmad4 genes in lung adenocarcinomas induced byN-nitrosobis(2-hydroxypropyl)amine in rats

Tsujiuchi, Toshifumi; Sasaki, Yasutaka; Tsutsumi, Masahiro; Konishi, Yoichi

doi:10.1002/1098-2744(200010)29:2<87::aid-mc5>3.0.co;2-r

Cited by 26 publications

(21 citation statements)

References 21 publications

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“…In conclusion, taken together with our previous findings (22,28), the results of this study show that alterations in the Smad4 gene might play a limited role during nitrosaminerelated carcinogenesis in rodents. We previously reported alterations in TGFß signaling pathway-associated genes, such as TGFß receptor II, Smad2 and mannose 6-phospate/insulinelike growth factor II receptor genes, in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (22,38,39), with tumor cells expressing higher levels of TGFß than normal lung tissue (40).…”

Section: Discussionsupporting

confidence: 87%

“…Thus, it has been suggested that inactivation of the Smad4 gene might play a role in pancreatic cancer and possibly other human cancers. In the case of rodents, we previously reported a low frequency of Smad4 mutations in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (8.3%) (22) and no mutations in rat hepatocellular carcinomas induced by Nnitrosodiethylamine (29). The present study showed only one mutation in 12 hamster PDAs and three established cell lines.…”

Section: Discussionsupporting

confidence: 47%

“…To determine the sequence of the open reading frame (ORF) and 5' upstream and 3' downstream regions, PCR amplifications were performed with primer sets based on the rat Smad4 cDNA sequence (GenBank accession no. AF170064) as described previously (22). The amplified products were separated on 2% NuSieve agarose gels (BMA, Rockland, ME) containing 0.05 μg/ml ethidium bromide and then extracted and directly sequenced using a BigDye Terminator v3.0 cycle sequencing ready reaction kit (Applied Biosystems Japan Ltd., Tokyo, Japan) and an ABI PRISM 310 genetic analyzer (Applied Biosystems Japan Ltd.).…”

Section: Animals and Treatmentmentioning

confidence: 99%

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Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Shimizu

Kitahashi²,

Fujii³

et al. 2006

Oncol Rep

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Abstract. Alterations of the Smad4 gene, identified as a mediator of the transforming growth factor-ß pathway, were investigated in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 12 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/12, 8.3%) in the form of an ACC to ATC (Thr to IIe) transition at codon 73; none were detected in the three cell lines. No reduced or increased expression of the Smad4 gene was detected in any case using real-time quantitative RT-PCR. These results suggest that the Smad4 gene might play a role in limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 47%

Section: Animals and Treatmentmentioning

confidence: 99%

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Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Shimizu

Kitahashi²,

Fujii³

et al. 2006

Oncol Rep

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“…RT-PCR-restriction-SSCP analysis was carried out using the primers listed as described earlier (unpublished results) 39) (Table I). All primers were designed from rat Smad2 and Smad4 cDNA sequences (GenBank accession numbers for TGF-βRII, Smad2 and Smad4 are L09653, AB010147 and AB010954, respectively).…”

Section: Animalsmentioning

confidence: 99%

Alterations of the Transforming Growth Factor‐(β Signaling Pathway in Hepatocellular Carcinomas Induced Endogenously and Exogenously in Rats

Sasaki

Tsujiuchi

Murata

et al. 2001

Japanese Journal of Cancer Research

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“…As it is possible to monitor the step-by-step development of lung malignancies with this model, the molecular mechanisms involved can be readily investigated. Taking advantage of this model, we have been able to accumulate data on genetic alterations during carcinogenesis including Ki-ras mutations 9 , alterations in genes associated with the transforming growth factor-β signaling pathway 10,11 and alterations in tumor suppressor genes located on human chromosome 3p [12][13][14][15] . Methylation of cytosine residues at CpG dinucleotides is characteristic of suppression of gene expression in mammalian genomes 16,17 .…”

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confidence: 99%

Reduced Expression of the Pcdh20 Gene and Its Aberrant DNA Methylation in Lung Adenocarcinomas Induced by N-nitrosobis(2-hydroxypropyl)amine in Rats

et al. 2008

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Protocadherins are a major subfamily of the cadherin superfamily that play an important role in communication between adjacent cells. To clarify the involvement of Protocadherin 20 (Pcdh20) gene in rat lung carcinogenesis, we investigated the expression of Pcdh20 and its methylation status in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). Six-week old male Wistar rats were given 2000 ppm BHP in their drinking water for 12 weeks and were maintained without further treatment until they were sacrificed after 25 weeks. Total RNAs were extracted from 7 lung adenocarcinomas, one from each BHP-treated rat, and the expression levels of Pcdh20 were measured using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Four out of 7 tumors showed reduced expression of Pcdh20, compared with 3 normal lung tissues. For methylation analysis, bisulfite sequencing was performed. The 5' upstream region of Pcdh20 was methylated in 4 adenocarcinomas with reduced expression of Pcdh20, but was unmethylated in normal lung tissue. These results suggest that aberrant methylation of the Pcdh20 gene might be involved in the development of lung adenocarcinomas induced by BHP in rats. (J Toxicol Pathol 2008; 21: 257-260)

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Mutations of theSmad2 andSmad4 genes in lung adenocarcinomas induced byN-nitrosobis(2-hydroxypropyl)amine in rats

Cited by 26 publications

References 21 publications

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Alterations of the Transforming Growth Factor‐(β Signaling Pathway in Hepatocellular Carcinomas Induced Endogenously and Exogenously in Rats

Reduced Expression of the Pcdh20 Gene and Its Aberrant DNA Methylation in Lung Adenocarcinomas Induced by N-nitrosobis(2-hydroxypropyl)amine in Rats

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