This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chandler, L A Articles by Bourgeois, S Search for Related Content PubMed PubMed Citation Articles by Chandler, L A Articles by Bourgeois, S

A novel mechanism of Ha-ras oncogene action: regulation of fibronectin mRNA levels by a nuclear posttranscriptional event.

Regulatory Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186-5800.

ABSTRACT

Although loss of cell surface fibronectin (FN) is a hallmark of many oncogenically transformed cells, the mechanisms responsible for this phenomenon remain poorly understood. The present study utilized the nontumorigenic human osteosarcoma cell line TE-85 to investigate the effects of induced Ha-ras oncogene expression on FN biosynthesis. TE-85 cells were stably transfected with metallothionein-Ha-ras fusion genes, and the effects of metal-induced ras expression on FN biosynthesis were determined. Induction of the ras oncogene, but not proto-oncogene, was accompanied by a decrease in total FN mRNA and protein levels. Transfection experiments indicated that these oncogene effects were not due to reduced FN promoter activity, suggesting that a posttranscriptional mechanism was involved. The most common mechanism of posttranscriptional regulation affects cytoplasmic mRNA stability. However, in this study the down-regulation of FN was identified as a nuclear event. A component of the ras effect was due to a mechanism affecting accumulation of processed nuclear FN RNA. Mechanisms that would generate such an effect include altered RNA processing and altered stability of the processed message in the nucleus. There was no effect of ras on FN mRNA poly(A) tail length or site of polyadenylation. There was also no evidence for altered splicing at the ED-B domain of FN mRNA. This demonstration of nuclear posttranscriptional down-regulation of FN by the Ha-ras oncogene identifies a new level at which ras oncoproteins can regulate gene expression and thus contribute to development of the malignant phenotype.

This article has been cited by other articles:

• Spano, D., Branchi, I., Rosica, A., Pirro, M. T., Riccio, A., Mithbaokar, P., Affuso, A., Arra, C., Campolongo, P., Terracciano, D., Macchia, V., Bernal, J., Alleva, E., Di Lauro, R. (2004). Rhes Is Involved in Striatal Function. Mol. Cell. Biol. 24: 5788-5796 [Abstract] [Full Text]  
• Mazzoni, E., Adam, A., Bal de Kier Joffe, E., Aguirre-Ghiso, J. A. (2003). Immortalized Mammary Epithelial Cells Overexpressing Protein Kinase C {gamma} Acquire a Malignant Phenotype and Become Tumorigenic in Vivo. Mol Cancer Res 1: 776-787 [Abstract] [Full Text]  
• Berkovich, E., Ginsberg, D. (2001). Ras Induces Elevation of E2F-1 mRNA Levels. J. Biol. Chem. 276: 42851-42856 [Abstract] [Full Text]  
• Graham, T. E., Key, T. A., Kilpatrick, K., Dorin, R. I. (2001). Dexras1/AGS-1, a Steroid Hormone-Induced Guanosine Triphosphate-Binding Protein, Inhibits 3',5'-Cyclic Adenosine Monophosphate-Stimulated Secretion in AtT-20 Corticotroph Cells. Endocrinology 142: 2631-2640 [Abstract] [Full Text]  
• Aguirre-Ghiso, J. A., Liu, D., Mignatti, A., Kovalski, K., Ossowski, L. (2001). Urokinase Receptor and Fibronectin Regulate the ERKMAPK to p38MAPK Activity Ratios That Determine Carcinoma Cell Proliferation or Dormancy In Vivo. Mol. Biol. Cell 12: 863-879 [Abstract] [Full Text]  
• Le, T., Leung, L., Carroll, W. L., Schibler, K. R. (1997). Regulation of Interleukin-10 Gene Expression: Possible Mechanisms Accounting for Its Upregulation and for Maturational Differences in Its Expression by Blood Mononuclear Cells. Blood 89: 4112-4119 [Abstract] [Full Text]  
• Ungefroren, H., Krull, N. B. (1996). Transcriptional Regulation of the Human Biglycan Gene. J. Biol. Chem. 271: 15787-15795 [Abstract] [Full Text]  
• Scita, G., Darwiche, N., Greenwald, E., Rosenberg, M., Politi, K., De Luca, L. M. (1996). Retinoic Acid Down-regulation of Fibronectin and Retinoic Acid Receptor alpha Proteins in NIH-3T3 Cells. J. Biol. Chem. 271: 6502-6508 [Abstract] [Full Text]