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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Alterations in the expression pattern of MTHFR, DHFR, TYMS, and SLC19A1 genes after treatment of laryngeal cancer cells with high and low doses of methotrexate

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Author(s):
Silva Galbiatti, Ana Livia [1] ; Castro, Rodrigo [1] ; Caldas, Heloisa Cristina [2] ; Padovani, Jr., Joao Armando [3] ; Pavarino, Erika Cristina [1] ; Goloni-Bertollo, Eny Maria [1]
Total Authors: 6
Affiliation:
[1] Sao Jose do Rio Preto Med Sch FAMERP, Genet & Mol Biol Res Unit UPGEM, Sao Jose Do Rio Preto, SP - Brazil
[2] Sao Jose do Rio Preto Med Sch FAMERP, Lab Expt Immunol & Transplantat LITEX, Sao Jose Do Rio Preto, SP - Brazil
[3] Sao Jose do Rio Preto Med Sch FAMERP, Otorhinolaryngol & Head & Neck Surg Dept, Sao Jose Do Rio Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: TUMOR BIOLOGY; v. 34, n. 6, p. 3765-3771, DEC 2013.
Web of Science Citations: 9
Abstract

Inter-individual variations to methotrexate (MTX) outcome have been attributed to different expression profiles of genes related to folate metabolism. To elucidate the mechanisms of variations to MTX outcome, we investigated MTHFR, DHFR, TYMS, and SLC19A1 gene expression profiles by quantifying the mRNA level of the genes involved in folate metabolism to MTX response in laryngeal cancer cell line (HEP-2). For this, three different concentrations of MTX (0.25, 25, and 75 mu mol) were added separately in HEP-2 cell line for 24 h at 37 A degrees C. Apoptotis quantification was evaluated with fluorescein isothiocyanate-labeled Bcl-2 by flow cytometry. Real-time quantitative PCR technique was performed by quantification of gene expression with TaqManA (R) Gene Expression Assay. ANOVA and Bonferroni's post hoc tests were utilized for statistical analysis. The results showed that the numbers of apoptotic HEP-2 cells with 0.25, 25.0, and 75.0 mu mol of MTX were 14.57, 77.54, and 91.58 %, respectively. We found that the expression levels for MTHFR, DHFR, TYMS, and SLC19A1 genes were increased in cells with 75.0 mu mol of MTX (p < 0.05). Moreover, SLC19A1 gene presented lower expression in cells treated with 0.25 mu mol of MTX (p < 0.05). In conclusion, our data suggest that MTHFR, DHFR, TYMS, and SLC19A1 genes present increased expression after the highest application of MTX dose in laryngeal cancer cell line. Furthermore, SLC19A1 gene also presents decreased expression after the lowest application of MTX dose in laryngeal cancer cell line. Significant alterations of expression of these studied genes in cell culture model may give support for studies in clinical practice and predict interesting and often novel mechanisms of resistance of MTX chemotherapy. (AU)

FAPESP's process: 10/12930-4 - Evaluation of chemotherapy, gene expression and proteins quantification in head and neck carcinoma
Grantee:Eny Maria Goloni Bertollo
Support Opportunities: Regular Research Grants
FAPESP's process: 10/12932-7 - Evaluation of chemotherapy, gene expression and proteins quantification in head and neck carcinoma
Grantee:Ana Lívia Silva Galbiatti-Dias
Support Opportunities: Scholarships in Brazil - Doctorate