Tel induces a G1 arrest and suppresses Ras-induced transformation.
The Tel gene is a major target of translocations in leukemia and loss of heterozygosity is regularly observed for the non-translocated allele, thus supporting the notion that Tel is a tumor suppressor. Most tumor suppressors influence cellular proliferation, differentiation and cell death and thereby prevent oncogenic transformation and genetic instability. We found that overexpression of Tel retards proliferation of many cell types, primary cells and immortalized cells, by inducing a G1 arrest. Tel's block of cellular proliferation is rescued by high seeding densities. Furthermore, Tel suppressed Ras-mediated colony growth in soft agar and tumor formation in nude mice. The Pointed and DNA binding (DB) domains of Tel were required for all Tel-induced phenotypes.
Rompaey
L V
LV
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, TN 38105, USA.
Potter
M
M
Adams
C
C
Grosveld
G
G
D016475:3T3 Cells; D000362:Agar; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016193:G1 Phase; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D000097764:ETS Translocation Variant 6 Protein
D000362:Agar; D004268:DNA-Binding Proteins; D015689:Oncogene Protein p21(ras); D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein