title: Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase.
abstract: We recently reported that forced overexpression of the transcription factor E2F-1 in human HT-1080 fibrosarcoma cells resulted in corresponding high levels of thymidylate synthase (TS) and resistance to 5-fluoropyrimidines (D. Banerjee et al., Cancer Res., 58: 4292-4296, 1998). Because colorectal metastasis to the lung has higher TS levels than liver metastasis and is less responsive to treatment with 5-fluorouracil (R. Gorlick et al., J. Clin. Oncol., 16: 1465-1469, 1998), it was, therefore, of interest to measure E2F-1 expression in these tumors. In contrast to marginally increased levels of dihydrofolate reductase and topoisomerase I in lung metastasis as compared with liver metastasis, lung tumors had a 5-fold increase in E2F-1 expression as compared with liver tumors, corresponding to the relative levels of TS in these metastases. These data indicate that there exists a close correlation between E2F-1 and TS levels and provide a rationale for targeting this transcription factor, ie., E2F-1, for the treatment of certain cancers.
authors.affiliation: Program of Molecular Pharmacology, Sloan Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: D
authors.initials: D
authors.lastname: Banerjee
authors.forename: R
authors.initials: R
authors.lastname: Gorlick
authors.forename: A
authors.initials: A
authors.lastname: Liefshitz
authors.forename: K
authors.initials: K
authors.lastname: Danenberg
authors.forename: P C
authors.initials: PC
authors.lastname: Danenberg
authors.forename: P V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: D
authors.initials: D
authors.lastname: Klimstra
authors.forename: S
authors.initials: S
authors.lastname: Jhanwar
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Y
authors.initials: Y
authors.lastname: Fong
authors.forename: N
authors.initials: N
authors.lastname: Kemeny
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003110:Colonic Neoplasms / Q000473:pathology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary*; D056465:Retinoblastoma-Binding Protein 1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D013940:Thymidylate Synthase