Alterations of lymphoid enhancer factor-1 isoform expression in solid tumors and acute leukemias

Wenbing Wang, Ping Ji, Björn Steffen, Ralf Metzger, Paul M. Schneider, Hartmut Halfter, Mark Schrader, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Two major transcripts of lymphoid enhancer factor-1 (LEF-1) have been described. The long isoform with β-catenin binding domain functions as a transcriptional enhancer factor. The short isoform derives from an intronic promoter and exhibits dominant negative activity. Recently, alterations of LEF-1 isoforms distribution have been described in colon cancer. In the current study we employed a quantitative real-time reverse transcription PCR method (TaqMan) to analyze expression of LEF-1 isoforms in a large cohort of human tumor (n=304) and tumor-free control samples (n=56). The highest expression level of LEF-1 was found in carcinoma samples whereas brain cancer samples expressed little. Expression of LEF-1 was different in distinct cancer types. For example, the mRNA level of LEF-1 was lower in testicular tumor samples compared with tumor-free control samples. Besides epithelial cancers, significant LEF-1 expression was also found in hematopoietic cells. In hematological malignancies, overall LEF-1 level was higher in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis. However, acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of the oncogenic LEF-1 compared with chronic lymphocytic leukemia and chronic myeloid leukemia. Taken together, these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalActa Biochimica et Biophysica Sinica
Volume37
Issue number3
StatePublished - Mar 1 2005
Externally publishedYes

Keywords

  • AML
  • Isoform
  • Lymphoid enhancer factor (LEF-1)
  • Solid tumor
  • β-catenin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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    Wang, W., Ji, P., Steffen, B., Metzger, R., Schneider, P. M., Halfter, H., Schrader, M., Berdel, W. E., Serve, H., & Müller-Tidow, C. (2005). Alterations of lymphoid enhancer factor-1 isoform expression in solid tumors and acute leukemias. Acta Biochimica et Biophysica Sinica, 37(3), 173-180.