Characterization and identification of PARM-1 as a new potential oncogene

• Published in: Molecular cancer Vol. 12; no. 1; p. 84
• Main Authors: Charfi, Cyndia, Levros, Jr, Louis-Charles, Edouard, Elsy, Rassart, Eric
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.07.2013; BioMed Central
• Subjects: Androgen-Binding Protein - genetics; Androgen-Binding Protein - metabolism; Animals; B cells; Cancer; Caveolin 1; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell growth; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Development and progression; Endosomes - metabolism; Flow cytometry; Gene Expression; Gene Expression Profiling; Genetic aspects; Golgi Apparatus - metabolism; Humans; Leukemia, T-Cell - genetics; Leukemia, T-Cell - metabolism; Lymphocytic leukemia; Medical research; Mice; Microscopy; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Mucins; Mutation; NIH 3T3 Cells; Oncogenes; Physiological aspects; Protein Binding; Protein Transport; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rodents; Signal Transduction; STAT3 Transcription Factor - metabolism; Tubulin - metabolism; Tumors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-12-84

The Graffi murine retrovirus is a powerful tool to find leukemia associated oncogenes. Using DNA microarrays, we recently identified several genes specifically deregulated in T- and B-leukemias induced by this virus. In the present study, probsets associated with T-CD8+ leukemias were analyzed and we validated the expression profile of the Parm-1 gene. PARM-1 is a member of the mucin family. We showed that human PARM-1 is an intact secreted protein accumulating predominantly, such as murine PARM-1, at the Golgi and in the early and late endosomes. PARM-1 colocalization with α-tubulin suggests that its trafficking within the cell involves the microtubule cytoskeleton. Also, the protein co-localizes with caveolin-1 which probably mediates its internalization. Transient transfection of both mouse and human Parm-1 cDNAs conferred anchorage- and serum-independent growth and enhanced cell proliferation. Moreover, deletion mutants of human PARM-1 without either extracellular or cytoplasmic portions seem to retain the ability to induce anchorage-independent growth of NIH/3T3 cells. In addition, PARM-1 increases ERK1/2, but more importantly AKT and STAT3 phosphorylation. Our results strongly suggest the oncogenic potential of PARM-1.