Expression of the growth arrest-specific gene 6 (GAS6) in leukemia and lymphoma cell lines

Leuk Res. 1999 Jul;23(7):643-51. doi: 10.1016/s0145-2126(99)00075-2.


The initial identification of GAS6 as a protein expressed in response to growth arrest suggested that it might function as a negative regulator of cell proliferation. Since the transforming activity of the GAS6 receptor (AXL/UFO) was documented, GAS6 might stimulate rather than inhibit proliferation. In order to detect aberrant expression of GAS6 we examined gene expression in 46 cell lines of precursor B-, B- and T-cell origin as well as from Hodgkin's disease and cell lines established from various myeloproliferative disorders. In our study, the expression of GAS6 reveals a constitutive transcriptional activation in 8/46 cases of proliferating cell lines. The GAS6 mRNA expression could be shown in 4/22 cell lines of the lymphoid arm and in 4/17 of the myeloid lineages of the hematopoietic system. No transcripts could be detected in the CD30+ Hodgkin and anaplastic large cell lymphomas (0/7). Interestingly, the steady state mRNA levels showed neglectable GAS6 expression in precursor B and B-cell lines (1/9), but could be detected in terminally differentiated plasma cell lines (4/4). The predominantly GAS6-expressing cell lines of non-lymphoid origin have been established from acute myeloid leukemias of the M4 subtype (3/4). In order to demonstrate evidence for an autocrine regulation of growth in permanent hematopoietic cell lines, we measured the GAS6 expression in cell lines with strong positivity for the AXL/UFO receptor mRNA. Constitutive basal levels of GAS6 mRNA and protein expression could be only detected in 3/23 AXL/UFO expressing cell lines. Although a general mechanism seems most unlikely, further studies are necessary to demonstrate the involvement of GAS6 in single cases of disordered growth or chemotaxis/adhesion of leukemia and lymphomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cell Division
  • Cell Line
  • Cloning, Molecular
  • Gene Expression Regulation, Leukemic
  • Gene Expression Regulation, Neoplastic*
  • Hematopoietic Stem Cells / metabolism
  • Hodgkin Disease / genetics
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Kidney
  • Leukemia / genetics*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Lymphocyte Subsets / metabolism
  • Lymphoma / genetics*
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / metabolism
  • Myeloproliferative Disorders / pathology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / metabolism
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics
  • Protein Biosynthesis*
  • Proteins / genetics
  • Proto-Oncogene Proteins
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Recombinant Fusion Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Oncogene Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • growth arrest-specific protein 6
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase