Characterization of Nuclear Factors that Bind to the Human Thymidylate Synthase Gene in HL-60 Cells Differentiated by All-trans Retinoic Acid Treatnent.

Horie, Nobutaka; Komada, Yukinori; Ueta, Yumiko; Suzuki, Tomoko; Nozawa, Ryushi; Takeishi, Keiichi

doi:10.1248/bpb.24.1351

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…Thymidylate synthase (TS) is an enzyme that synthesizes thymidylate de novo and its expression is tightly correlated with cell growth. 19) As shown in Fig. 2, the expression of TS declined markedly during the differentiation.…”

Section: Expression Of Cdk Inhibitors During the Differentiation Of Hmentioning

confidence: 73%

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Implication of CDK Inhibitors p21 and p27 in the Differentiation of HL-60 Cells

Horie

Mori

Asada

et al. 2004

Biological & Pharmaceutical Bulletin

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Section: Expression Of Cdk Inhibitors During the Differentiation Of Hmentioning

confidence: 73%

“…19) HL-60 cells were treated with 10 Ϫ6 M ATRA and the changes in the expression of growth-related genes were examined by Northern blotting. The results were shown in Fig.…”

Section: Expression Of Cdk Inhibitors During the Differentiation Of Hmentioning

confidence: 99%

Implication of CDK Inhibitors p21 and p27 in the Differentiation of HL-60 Cells

Horie

Mori

Asada

et al. 2004

Biological & Pharmaceutical Bulletin

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“…The TS mRNA levels Expression of the TS gene can be controlled by many factors, including E2F1, 64 p53, 65 c-myc, 66 autoregulation, 67 rTS 68 and nuclear factors (NF-TS). 69 Expression of the TS gene has also been shown to be dependent on MSI. For example, the present study, which is in agreement with Ricciardiello et al, 24 Calascibetta et al, 70 and Jensen et al, 71 shows that cancers with MSI have higher levels of TS protein than MSS tumours.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Thymidylate Synthase Gene Variants, RNA and Protein Levels in Primary Colorectal Adenocarcinomas

et al. 2010

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This study was designed to compare thymidylate synthase (TS) genotype, mRNA and protein levels in primary colorectal adenocarcinoma, and to examine the correlation between microsatellite instability (MSI) and TS expression. The TS genotype of 68 patients with colorectal cancer was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis in peripheral blood mononuclear cells and tumour tissue. The TS mRNA levels in tumour tissue were measured by reverse-transcription PCR, and TS protein levels and MSI status were assessed using immunohistochemistry. Significantly higher mRNA and protein levels were observed in patients with the TS 3R/3R versus the 2R/2R and 2R/3R genotypes. There was no correlation between TS single nucleotide polymorphism and TS expression. Individuals homozygous for the six base-pair insertion in the 3'-untranslated region had significantly higher TS mRNA levels than heterozygous and homozygous wild type individuals. The TS mRNA and protein levels were significantly higher in microsatellite unstable tumours compared with microsatellite stable tumours. There was a significant association between the number of TS enhancer region repeats (in blood) and intratumoural TS mRNA and protein levels. A larger case series investigating the role of TS gene polymorphisms as predictors of sensitivity to 5-fluorouracil-based chemotherapy is required.

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“…The expression of TS mRNA can be controlled by many factors, including E2F, 19) rTS 20) and NF-TS3. 21) The influence of TS genotype on mRNA expression might be masked by the variations of these factors among different population groups.…”

Section: Discussionmentioning

confidence: 99%

Functional Polymorphism of the Thymidylate Synthase Gene in Colorectal Cancer Accompanied by Frequent Loss of Heterozygosity

Kawakami

Ishida

Danenberg

et al. 2002

Japanese Journal of Cancer Research

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The thymidylate synthase (TS) gene has a polymorphic repeated sequence in its 5′ ′ ′ ′-untranslated region. The repeat length is associated with TS protein expression, which suggests that we may be able to predict the efficacy of 5-fluorouracil (5-FU)-based chemotherapy from a patient's TS Key words: Thymidylate synthase -Loss of heterozygosity -Gene polymorphism -Pharmacogenomics -Cancer chemotherapy Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP by 5,10-methylenetetrahydrofolate to form dTMP and dihydrofolate. TS has been an important target for cancer chemotherapy because of its central, rate-limiting role in the de novo synthesis of dTTP. 1) 5-Fluorouracil (5-FU) inhibits TS by forming a stable ternary complex among 5,10-methylenetetrahydrofolate, TS and fluoro-dUMP, the metabolite of 5-FU. Based on this mechanism, the TS expression level in cancer tissue has been expected to be a predictor of response to 5-FU-based chemotherapy, and indeed, recent studies have shown that the sensitivity of various tumors to 5-FU-based chemotherapy is associated with the intratumoral level of TS. 2-5)The TS gene is known to have a unique tandemly repeated sequence in the 5′-untranslated region (5′-UTR) and is polymorphic in the numbers of this repeat.6) The double (2R) or the triple (3R) repeats are the most common, although higher numbers are also found less frequently. We previously reported that this polymorphism was associated with TS protein expression in human gastrointestinal cancers.7) The cancer tissue with 3R/3R genotype showed significantly higher TS protein expression than did that with 2R/3R genotype. This association between TS genotype and TS expression, together with the role of TS expression in 5-FU-based chemotherapy, suggest that the TS genotype might be a novel predictor of efficacy for 5-FU-based chemotherapy. Some clinical evidence has been reported to support this potential of the TS genotype, [8][9][10][11] although the studies had relatively small numbers of subjects, and validation by a larger-scale clinical study is needed.One of advantages of clinical use of TS genotype would be that the genotype can be determined through a blood test, and so the strategy would be applicable to patients with cancer that is not easily accessible. This expectation is based on the assumption that the genotype in normal tissue, i.e. peripheral blood cells, is identical with that in cancer tissue. However, this assumption has not yet been validated in the case of the TS genotype. Theoretically, the TS genotype in cancer tissue could be changed by genetic alterations, including instability of repeat length and allelic loss. To test this possibility, we analyzed the TS genotype

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Characterization of Nuclear Factors that Bind to the Human Thymidylate Synthase Gene in HL-60 Cells Differentiated by All-trans Retinoic Acid Treatnent.

Cited by 3 publications

References 28 publications

Implication of CDK Inhibitors p21 and p27 in the Differentiation of HL-60 Cells

Implication of CDK Inhibitors p21 and p27 in the Differentiation of HL-60 Cells

Correlation between Thymidylate Synthase Gene Variants, RNA and Protein Levels in Primary Colorectal Adenocarcinomas

Functional Polymorphism of the Thymidylate Synthase Gene in Colorectal Cancer Accompanied by Frequent Loss of Heterozygosity

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