Article: article from journal or magazin.
Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer
PT - Journal Article PT - Research Support, Non-U.S. Gov't
The human gene, human giant larvae (Hugl-1/Llg1/Lgl1) has significant homology to the Drosophila tumour suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that binds Myosin II and is involved in maintaining cell polarity and epithelial integrity. The human protein, Hugl-1 contains several conserved functional domains found in Lgl, suggesting that these proteins may have closely related functions. Whether loss of Hugl expression plays a role in human tumorigenesis has so far not been extensively investigated. Thus, we evaluated tumour tissues from 94 patients undergoing surgery for colorectal cancer (CRC) for loss of Hugl-1 transcription and compared our findings with the clinical data from each of these patients. We found that Hugl-1 was lost in 75% of tumour samples and these losses were associated with advanced stage and particularly with lymph node metastases. Reduced Hugl-1 expression during the adenoma-carcinoma sequence occurring as early as in colorectal adenomas was detected by both immunohistochemical and reverse transcription-polymerase chain reaction analysis. Functional assays with ecdysone-inducible cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Our studies thus indicate that downregulation of Hugl-1 contributes to CRC progression
Adenoma/metabolism/Adult/Animals/Blotting,Western/Caco-2 Cells/Carcinoma/Cell Adhesion/Cell Cycle/Cell Differentiation/Cell Line/Cell Line,Tumor/Cell Movement/Colorectal Neoplasms/Cytoskeletal Proteins/Cytoskeleton/Disease Progression/Down-Regulation/Drosophila Proteins/Drosophila melanogaster/Female/Gene Expression Regulation,Neoplastic/Green Fluorescent Proteins/Humans/Immunohistochemistry/Intestinal Mucosa/Male/Microscopy,Fluorescence/Middle Aged/Neoplasms/Protein Structure,Tertiary/Proteins/genetics/Reverse Transcriptase Polymerase Chain Reaction/Transcription,Genetic/Tumor Suppressor Proteins
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