Activation of HMGI-C gene and its significance in well-differentiated liposarcomas

点击翻译按钮获取中文摘要

In order to elucidate the molecular mechanism involved in the development and progression of well-differentiated liposarcoma, expression of HMGI-C, molecular mechanism of the activation of HMGI-C gene and functions of HMGI-C in the transformation of fibroblasts were investigated as followings :1. Expressions of HMGI-C gene at both protein and message levels :(1) Immunohistochemical and Western blot analyses(2) Analysis by in situ hybridization (ISH)2. Molecular mechanism of the activation of HMGI-C gene :(1) nested reverse transcription polymerase chain reaction (nested RT-PCR)and DNA sequencing(2) Southern blot analysis for gene amplification(3) 3' rapid amplifiction of cDNA ends (3'RACE) for chimera gene formation3. In vitro transformation studies using fibroblasts derived from HMGI-C-/- or HMGI-C +/+ mouseTumor cells of well differentiated liposarcoma overexpressed HMGI-C gene (21/21 cases). In contrast, dedifferentiated liposarcomas, which developed in well-differentiated liposarco … More ma and are highly malignant, showed loss of HMGI-C expressions. No abnormality was disclosed in the moleular weight of HMGI-C protein expressed in well-differentiated liposarcomas or in cDNA of protein coding region of HMGI-C gene demonstrated by nested RT-PCR.Southern blot analysis did not show any amplification of HMGI-C gene in well differentiated liposarcomas. 3'RACE analysis has not demonstrated any newly formed chimera gene of HMGI-C in well-differentiated liposarcoma so far. In vitro studies showed that fibroblasts derived from HMGI-C -/- mouse transformed more frequently than those derived from HMGI-C -/- mouse, and the transformation in HMGI-C -/- fibroblasts was inhibited by transfection of HMGI-C cDNA.These data clearly demonstrated that activation of HMGI-C gene is involved in the development and progression of well-differentitated liposarcoma. Both in vivo and in vitro data indicated that HMGI-C overexpressed in well-differentiated liposarcomas may inhibit progression to highly malignant tumor, i.e. dedifferentiated liposarcoma. The present data suggested that abnormalies in 3' UTR AUUUA motifs and / or promotor resion might contribute to the activation of HMGI-C in well- differentiated liposarcomas. Less