H Edamatsu1, Y Kaziro, H Itoh. 1. Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Abstract
BACKGROUND: The proliferation of mammalian cells is controlled by various intracellular mitogenic signalling pathways. In the intracellular pathways, Ras is involved in the activation of proto-oncogenes such as an immediate early gene c-fos. The somatic mutations of ras genes that elicit the constitutive activation of Ras have been found in tumours. Although these findings suggest that the constitutive activation of Ras-mediated pathways alters the expression of a set of genes involving tumorigenesis, these genes have not yet fully been studied. RESULTS: To study the up- or down-regulated genes in ras-transformed cells, we analysed Rat-1 transfectants expressing Ras(G12V) mutant protein in response to isopropyl-1-beta-thio-D-galactoside using a differential display. We found that the mRNA level of rat homologue of LUCA15, which has been cloned initially as a putative tumour suppressor gene mapped on human chromosome 3, was down-regulated by the expression of Ras(G12V). Epitope-tagged LUCA15 protein was localized in nuclei and had the ability to bind poly(G) RNA homopolymers in vitro. Moreover, ectopic expression of LUCA15 in human fibrosarcoma HT1080 cells suppressed the cell growth. CONCLUSION: These results demonstrate that LUCA15 is one of the down-regulated genes in ras-transformed cells, and suggests that LUCA15 may function as a negative regulator of cell proliferation by the alteration of its mRNA level.
BACKGROUND: The proliferation of mammalian cells is controlled by various intracellular mitogenic signalling pathways. In the intracellular pathways, Ras is involved in the activation of proto-oncogenes such as an immediate early gene c-fos. The somatic mutations of ras genes that elicit the constitutive activation of Ras have been found in tumours. Although these findings suggest that the constitutive activation of Ras-mediated pathways alters the expression of a set of genes involving tumorigenesis, these genes have not yet fully been studied. RESULTS: To study the up- or down-regulated genes in ras-transformed cells, we analysed Rat-1 transfectants expressing Ras(G12V) mutant protein in response to isopropyl-1-beta-thio-D-galactoside using a differential display. We found that the mRNA level of rat homologue of LUCA15, which has been cloned initially as a putative tumour suppressor gene mapped on human chromosome 3, was down-regulated by the expression of Ras(G12V). Epitope-tagged LUCA15 protein was localized in nuclei and had the ability to bind poly(G) RNA homopolymers in vitro. Moreover, ectopic expression of LUCA15 in humanfibrosarcoma HT1080 cells suppressed the cell growth. CONCLUSION: These results demonstrate that LUCA15 is one of the down-regulated genes in ras-transformed cells, and suggests that LUCA15 may function as a negative regulator of cell proliferation by the alteration of its mRNA level.
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