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

来源 :Acta Biochimica et Biophysica Sinica | 被引量 : 0次 | 上传用户:vikdl
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Two major transcripts of lymphoid enhancer factor-1(LEF-1)have been described.The longisoform with β-catenin binding domain functions as a transcriptional enhancer factor.The short isoformderives from an intronic promoter and exhibits dominant negative activity.Recently,alterations of LEF-1isoforms distribution have been described in colon cancer.In the current study we employed a quantitativereal-time reverse transcription PCR method(TaqMan)to analyze expression of LEF-1 isoforms in a largecohort of human tumor(n=304)and tumor-free control samples(n=56).The highest expression level ofLEF-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 testiculartumor samples compared with tumor-free control samples.Besides epithelial cancers,significant LEF-1expression was also found in hematopoietic cells.In hematological malignancies,overall LEF-1 level washigher in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis.However,acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of theoncogenic LEF-1 compared with chronic lymphocytic leukemia and chromc myeloid leukemia.Taken together,these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic andthe dominant negative short isoform altered not only in carcinomas but also in leukemia. 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 isoformderives from an intronic promoter and exhibits dominant negative activity. LEF-1 isoforms distribution have been described in colon cancer. 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- The highest expression level of LEF-1 was found in carcinoma samples while 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 testiculartumor samples compared with tumor-free control samples .esides epithelial cancers, significant LEF-1 expression was also found in hematopoietic cells. In hematological malignancies, overall LEF-1 level washighe r in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis. However, acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of theoncogenic LEF-1 compared with chronic lymphocytic leukemia and chromc 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 not only in carcinomas but also in leukemia.
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