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.
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.
Banerjee
D
D
Program of Molecular Pharmacology, Sloan Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Gorlick
R
R
Liefshitz
A
A
Danenberg
K
K
Danenberg
P C
PC
Danenberg
P V
PV
Klimstra
D
D
Jhanwar
S
S
Cordon-Cardo
C
C
Fong
Y
Y
Kemeny
N
N
Bertino
J R
JR
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*
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