Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer

Spinola, Monica; Galvan, Antonella; Pignatiello, Carmen; Conti, Bárbara; Pastorino, Ugo; Nicander, Björn; Paroni, Rita; Dragani, Tommaso A.

doi:10.1038/sj.onc.1208687

Cited by 78 publications

(84 citation statements)

References 27 publications

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“…The lack of CK modification in tRNA-IPT mutants causes the destabilisation of the codon-anticodon interactions and codon context sensitivity (Caillet and Droogmans 1988). In mammals, the alterations in tRNA modification have been related to cancer, and the human tRNA-IPT gene (TRIT1) was identified as a candidate tumour suppressor negatively regulating lung carcinogenesis (Spinola et al 2005).…”

Section: Cks As a Part Of The Trna Of Phylogenetically Distinct Organmentioning

confidence: 99%

Cytokinins - recent news and views of evolutionally old molecules

Spíchal¹

2012

Functional Plant Biol.

156

169

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Cytokinins (CKs) are evolutionally old and highly conserved low-mass molecules that have been identified in almost all known organisms. In plants, they evolved into an important group of plant hormones controlling many physiological and developmental processes throughout the whole lifespan of the plant. CKs and their functions are, however, not unique to plants. In this review, the strategies and mechanisms of plants – and phylogenetically distinct plant-interacting organisms such as bacteria, fungi, nematodes and insects employing CKs or regulation of CK status in plants – are described and put into their evolutionary context. The major breakthroughs made in the last decade in the fields of CK biosynthesis, degradation and signalling are also summarised.

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Section: Cks As a Part Of The Trna Of Phylogenetically Distinct Organmentioning

confidence: 99%

Cytokinins - recent news and views of evolutionally old molecules

Spíchal¹

2012

Functional Plant Biol.

156

169

View full text Add to dashboard Cite

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“…Thus, direct sequencing of genomic DNA of 24 patients to identify SNPs with a frequency of the rare allele >0.02 confirmed the presence of the known TRIT1 coding polymorphisms rs3845570 (Pro11Pro) and rs3738671 (Phe202Leu) mapping in exon 1 and 5, respectively, but did not identify new coding variations in this gene (Table 2). SNP rs3845570 is a synonymous coding SNP (Pro11Pro) in exon 1 of the TRIT1 gene; however, in the shorter lung-specific isoform (AY702933), the rs3845570 SNP is located in the 5 -UTR region, 25-bp upstream the alternative ATG codon [12]. Coding SNPs were not detected in MFSD2.…”

Section: Trit1 Phe202leu Is Associated With Patients' Survivalmentioning

confidence: 99%

“…We previously showed that TRIT1 mRNA is expressed in normal lung with a complex pattern of alternatively spliced variants and that its expression levels are downregulated ∼6-to 14-fold in lung tumour tissue [12]. Similar analysis of MYCL1 and MFSD2 using quantitative real-time PCR on pools of normal and tumour lung tissue revealed no detectable MYCL1 mRNA levels in either normal or ADCA tissue, suggesting that MYCL1 is not a likely lung cancer progression modifier gene, whereas MFSD2 was expressed in normal lung parenchyma and downregulated in lung ADCA tissue.…”

Section: Trit1 and Mfsd2 Are Downregulated In Lung Adcasmentioning

confidence: 99%

“…TRIT1 encodes tRNA isopentenyltransferase, which catalyzes the formation of the modified base N 6 -isopentenyladenosine (i 6 A) in position 37 of tRNA molecules that bind codons starting with uridine [11,12]. TRIT1 alleles were tested for functional activity in the yeast strain MT-8, which has defective tRNA-isopentenyltransferase activity and synthesizes tRNAs lacking the isopentenyl-adenosine (i 6 A) modification, as compared with yeast strain H57, which produces an active tRNA-isopentenyltransferase gene.…”

Section: Assay For Isopentenyladenosine Activity Of Trit1 Allelesmentioning

confidence: 99%

“…TRIT1 alleles were tested for functional activity in the yeast strain MT-8, which has defective tRNA-isopentenyltransferase activity and synthesizes tRNAs lacking the isopentenyl-adenosine (i 6 A) modification, as compared with yeast strain H57, which produces an active tRNA-isopentenyltransferase gene. Yeast transformation and i 6 A analysis were carried out as described [12]. The TRIT1 Phe202 allele was obtained by amplification of a cDNA pool of normal lung tissue with primers 5 -caacggaccctacctcttgt-3 and 5 -cacctttccaaaggccact-3 and cloned into the yeast expression vector pYES2.1/V5-His-TOPO (Invitrogen).…”

Section: Assay For Isopentenyladenosine Activity Of Trit1 Allelesmentioning

confidence: 99%

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Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

et al. 2007

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Summary Linkage disequilibrium (LD) analysis to refine a region associated with lung cancer progression on chromosome 1p34 identified a 106 kb LD block that includes MYCL1, TRIT1 (tRNA isopentenyltransferase 1) and MFSD2 (major facilitator superfamily domain-containing 2). Caseonly association study on SNPs mapping in TRIT1 and MFSD2 indicated that the rare Leu allele (frequency: 0.04) of the TRIT1 Phe202Leu variation predicts short survival as compared to the common Phe/Phe genotype (hazard ratio (HR) = 1.7; 95% CI, 1.03-2.86; P = 0.039) in 335 Italian lung adenocarcinoma samples. A replication study in an independent population of 246 Norwegian lung cancer patients confirmed the significant association of the Phe202Leu polymorphism with patients' survival, but the rare allele was associated with better survival rate (HR = 0.5; 95% CI, 0.26-0.91; P = 0.023). The rare allele of TRIT1 Phe202Leu SNP was ∼seven-fold more frequent in Asian than in Caucasian subjects and three additional SNPs in the TRIT1 and MFSD2 genes showed ethnic differences in allelic frequencies. These results suggest that polymorphisms in the MYCL1 LD region affect lung cancer survival but that the functional element(s) may show population-specific patterns.

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N6‐isopentenyladenosine: A potential therapeutic agent for a variety of epithelial cancers

Spinola

Colombo

Falvella

et al. 2007

Intl Journal of Cancer

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Isopentenyladenosine (i6A) is a product of isopentenyltransferases and, in mammals, occurs either bound to tRNA or as a free nucleoside. Sporadic reports have suggested an anticancer effect of i6A, mostly on leukemia cells. The present analysis of 9 human epithelial cancer cell lines derived from different types of malignant tissue revealed complete suppression of clonogenic activity in 8 of the lines after exposure to i6A at a concentration of 10 μM. Mechanistic studies showed that i6A tumor suppressor activity is associated with inhibition of cell proliferation, a block in DNA synthesis and morphological changes. These results point to i6A and to its possible derivatives as a new potential class of wide‐spectrum anticancer agents. © 2007 Wiley‐Liss, Inc.

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Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer

Cited by 78 publications

References 27 publications

Cytokinins - recent news and views of evolutionally old molecules

Cytokinins - recent news and views of evolutionally old molecules

Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

N6‐isopentenyladenosine: A potential therapeutic agent for a variety of epithelial cancers

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