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