mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma Journal Article
| Authors: | Sowers, R.; Toguchida, J.; Qin, J.; Meyers, P. A.; Healey, J. H.; Huvos, A.; Banerjee, D.; Bertino, J. R.; Gorlick, R. |
| Article Title: | mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma |
| Abstract: | Previous studies have shown that decreased expression of the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR) are associated with intrinsic and acquired methotrexate resistance, respectively, in osteosarcoma (OS). It has also been shown in colorectal cancer that E2F-1 expression correlates with thymidylate synthase (TS) and, to a lesser extent, DHFR expression. To begin to investigate the regulation of DHFR and RFC expression in OS samples, mRNA expression of E2F-1 and E2F-4 were measured in OS tumor samples and related to DHFR, RFC, and TS mRNA expression. Using fluorescent quantitative real-time PCR, 112 human OS patient samples were investigated for potential E2F-1/E2F-4:DHFR, E2F-1/E2F-4:RFC, and E2F-1/E2F-4:TS correlations. The expression ranges for each gene are as follows: DHFR, 0.02-33.13 (median = 0.20); RFC, 0.02-229.13 (median = 1.91); TS, 0.01-9.99 (median = 0.15); E2F-1, 0.05-69.07 (median = 0.52); and E2F-4, 0.24-52.35 (median = 1.45). Spearman correlation coefficients (rs) for E2F-1:DHFR, E2F-1:RFC, E2F-1:TS, E2F-4:DHFR, E2F-4:RFC, and E2F-4:TS were calculated to be 0.53, 0.63, 0.60, 0.41, 0.58, and 0.33, respectively (P < 0.001). On the basis of this data, moderate correlations exist between E2F-1/E2F-4 and DHFR, RFC, and TS. These results suggest E2F-1/E2F-4 may play a role in the regulation of RFC expression, which has not been reported previously. The E2F transcription factors are also related to DHFR and TS expression in OS samples, suggesting a possible involvement in methotrexate resistance. Although E2F mRNA levels correlate with DHFR, RFC, and TS mRNA expression, additional experiments are necessary to determine the direct effects of these transcription factors and identify other proteins that may influence this relationship. © 2003 American Association for Cancer Research. |
| Keywords: | osteosarcoma; adolescent; adult; child; preschool child; aged; child, preschool; middle aged; carrier protein; dna binding protein; dna-binding proteins; methotrexate; cell cycle protein; metabolism; cell cycle proteins; reverse transcription polymerase chain reaction; transcription factor; drug resistance; enzymology; drug resistance, neoplasm; transcription factors; rna; biosynthesis; chemistry; dna; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; transcription factor e2f; carrier proteins; dihydrofolate reductase; thymidylate synthase; tetrahydrofolate dehydrogenase; transcription factor e2f1; membrane transport proteins; e2f1 transcription factor; reduced folate carrier; e2f transcription factors; transcription factor e2f4; humans; human; male; female; article; e2f1 protein, human; e2f4 protein, human; e2f4 transcription factor |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 2 |
| Issue: | 6 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2003-06-01 |
| Start Page: | 535 |
| End Page: | 541 |
| Language: | English |
| PUBMED: | 12813132 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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