Expression of the growth arrest-specific gene 6 (GAS6) in leukemia and lymphoma cell lines.
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.
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig. wdi@dsmz.de
W
W
Dirks
D
D
Rome
F
F
Ringel
K
K
Jäger
R A
RA
MacLeod
H G
HG
Drexler
D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722289:AXL protein, human