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

Debabrata Banerjee, Richard Gorlick, Anna Liefshitz, Kathy Danenberg, Peter C. Danenberg, Peter V. Danenberg, David Klimstra, Suresh Jhanwar, Carlos Cordon-Cardo, Yuman Fong, Nancy Kemeny, Joseph R. Bertino

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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, i.e., E2F-1, for the treatment of certain cancers.

Original languageEnglish (US)
Pages (from-to)2365-2367
Number of pages3
JournalCancer research
Volume60
Issue number9
StatePublished - May 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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