title: The novel gene EG-1 stimulates cellular proliferation.
abstract: We recently discovered a novel gene and named it endothelial-derived gene 1 (EG-1). Previously, we have shown that the expression of EG-1 is significantly elevated in the epithelial cells of breast cancer, colorectal cancer, and prostate cancer. Here, we report that EG-1 can stimulate cellular proliferation. Transfection experiments which overexpressed the full-length EG-1 gene in human embryonic kidney HEK-293 cells or human breast cancer cell lines resulted in significantly increased in vitro proliferation, in comparison with transfection with empty vectors. On the other hand, small interfering RNA cotransfection resulted in inhibition of proliferation. S.c. xenograft assays were carried out in a severe combined immunodeficient mouse model. We found that injection of high EG-1 expressing HEK-293 clones resulted in significantly larger tumors, in comparison with clones carrying the empty vectors. To further clarify the function of this gene, we investigated its interaction with Src and members of the mitogen-activated protein kinase (MAPK) family. Immunoprecipitation with anti-Src antibody, followed by immunoblotting with anti-EG-1 antibody, showed an association between these two molecules. Overexpression of EG-1 was correlated with activation of the following kinases: extracellular signal-regulated kinases 1 and 2, c-jun-NH2-kinase, and p38. These observations collectively support the hypothesis that the novel gene EG-1 is a positive stimulator of cellular proliferation, and may possibly be involved in signaling pathways involving Src and MAPK activation.
authors: Department of Surgery, Division of Oncology, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors: Ming
authors: M
authors: Lu
authors: Liping
authors: L
authors: Zhang
authors: Raymond Scott
authors: RS
authors: Maul
authors: Maryam R
authors: MR
authors: Sartippour
authors: Andrew
authors: A
authors: Norris
authors: Julian
authors: J
authors: Whitelegge
authors: Jian Yu
authors: JY
authors: Rao
authors: Mai N
authors: MN
authors: Brooks
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000081247:CSK Tyrosine-Protein Kinase; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D056892:Mediator Complex; D051379:Mice; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000235:genetics; D010770:Phosphotransferases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous; D019061:src-Family Kinases
chemical_list: C496877:MED28 protein, human; D056892:Mediator Complex; D010446:Peptide Fragments; D011506:Proteins; D011518:Proto-Oncogene Proteins; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D020928:Mitogen-Activated Protein Kinases