Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylatesynthase

We recently reported that forced overexpression of the transcription factor E2F-1 in human HT-1080 fibrosarcoma cells resulted in corresponding high l evels of thymidylate synthase (TS) and resistance to 5-fluoropyrimidines (D . Banerjee et at, Cancer Res., 58: 4292-4296, 1998). Because colorectal met astasis to the lung has higher TS levels than liver metastasis and is less responsive to treatment with 5-fluorouracil (R. Gorlick et at, J. Clin. Onc ol., 16: 1465-1469, 1998), it was, therefore, of interest to measure E2F-1 expression in these tumors. In contrast to marginally increased levels of d ihydrofolate reductase and topoisomerase I in lung metastasis as compared w ith 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 correlat ion between E2F-1 and TS levels and provide a rationale for targeting this transcription factor, i.e., E2F-1, for the treatment of certain cancers.