Possible involvement of MSX-2 homeoprotein in v-ras-induced transformation.
A truncated MSX-2 homeoprotein was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in untransformed cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a full-length human MSX-2 cDNA and tested its activities in two cell systems: fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated MSX-2 cDNA interfered with the transforming activities of both v-Ki-ras and v-raf oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and truncated MSX-2 cDNA was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that the truncated version MSX-2 may act as a dominant suppressor of intact MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.
Takahashi
C
C
Department of Molecular Oncology, Kyoto University School of Medicine, Japan.
Akiyama
N
N
Kitayama
H
H
Takai
S
S
Noda
M
M
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011905:Genes, ras; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal; D017570:MyoD Protein / Q000096:biosynthesis; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D027384:Oncogene Proteins v-raf; D009857:Oncogenes; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D017570:MyoD Protein; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D027384:Oncogene Proteins v-raf; D015689:Oncogene Protein p21(ras)