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ISSN 1672-9145 Acta Biochim Biophys Sin 2005, 37(3): 173–180 CN 31-1940/Q

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Alterations of Lymphoid Enhancer Factor-1 Isoform Expression in Solid Tumors and Acute Leukemias

Wenbing WANG¹, Ping JI²*, Björn STEFFEN², Ralf METZGER³, Paul M. SCHNEIDER³, Hartmut HALFTER⁴, Mark SCHRADER⁵, Wolfgang E. BERDEL², Hubert SERVE², and Carsten MÜLLER-TIDOW²*

¹Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China;

²Hematology and Oncology, and ³Neurology, Department of Medicine, University of Münster, D-48129 Münster, Germany;

⁴Department of Visceral and Vascular Surgery, University of Cologne, D-50931 Cologne, Germany;

⁵Department of Urology, Free University Berlin, D-12200 Berlin, Germany

Abstract Two major transcripts of lymphoid enhancer factor-1 (LEF-1) have been described. The long isoform with b-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.

Key words AML; b-catenin; isoform; lymphoid enhancer factor (LEF-1); solid tumor

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Received: October 25, 2004 Accepted: January 13, 2005

This work is supported by grants from the José-Carreras Leukemia Foundation, the Deutsche Forschungsgemeinschaft (Mu 1328/2-3, Se 600/2-2, SFB293), the Deutsche Krebshilfe (10-1819-Mü2), the IZKF (Interdisziplinäres Zentrum für Klinische Forschung) at the University of Münster, and the Fund of Jiangsu University

*Corresponding authors:

Ping JI: Tel, +49-251-835-2994; Fax, +49-251-835-2673; E-mail, [email protected]

Carsten MÜLLER-TIDOW: Tel, +49-251-835-2995; Fax, +49-251-835-2673; E-mail, [email protected]