The Ras-related protein AGS1/RASD1 suppresses cell growth.
AGS1/RASD1 is a Ras-related protein identified as a dexamethasone-inducible cDNA and as a signal regulator in various functional and protein-interaction screens. As an initial approach to define the role of AGS1/RASD1 as a Ras-family member, we determined its influence on cell growth/survival. In clonogenic assays with NIH-3T3 murine fibroblast cells, the MCF-7 human breast cancer cell line and the human lung adenocarcinoma cell line A549, AGS1/RASD1 markedly diminished the number of G418-resistant colonies, whereas the Ras subgroup member K-Ras was without effect. A549 cell infection with adenovirus engineered to express AGS1/RASD1 (Ad.AGS1) inhibited log phase growth in vitro and increased the percentage of cells undergoing apoptosis. The anti-growth action was also observed in vivo as the expression of AGS1/RASD1 inhibited the subcutaneous tumor growth of A549 cells in athymic nude mice. These data indicate that AGS1/RASD1, a member of the Ras superfamily of small G-proteins that often promotes cell growth and tumor expansion, plays an active role in preventing aberrant cell growth.
Vaidyanathan
Govindan
G
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Cismowski
Mary J
MJ
Wang
Guoshun
G
Vincent
Timothy S
TS
Brown
Kevin D
KD
Lanier
Stephen M
SM
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D037342:Pertussis Toxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism / Q000502:physiology*
C400132:RASD1 protein, human; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C498511:Rasd1 protein, mouse; D018631:ras Proteins