PMID- 7624154 OWN - NLM STAT- MEDLINE DCOM- 19950831 LR - 20131121 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 11 IP - 2 DP - 1995 Jul 20 TI - The Ras suppressor RSU-1 localizes to 10p13 and its expression in the U251 glioblastoma cell line correlates with a decrease in growth rate and tumorigenic potential. PG - 397-403 AB - Rsu-1, which was isolated based on its ability to suppress transformation by v-Ras, is a highly conserved gene which shares homology with yeast adenylyl cyclase in the region required for activation by Ras. Genomic DNA clones of human RSU-1 have been isolated and used as a probe for fluorescence in situ hybridization (FISH) to assign RSU-1 to 10p13, confirming the previous results of somatic cell hybrid mapping localizing RSU-1 to chromosome 10. Screening of more than 20 human tumor cell lines for RSU-1 expression revealed that most cell lines contained abundant RSU-1 RNA and protein. However, the p33 RSU-1 protein was undetectable in the U251 glioblastoma cell line and transfection of a rsu-1 expression vector into U251 cells yielded a cell line in which rsu-1 was under the control of a regulatable metallothionein promoter. Addition of Cd2+ to the U251-Rsu-1 transfectant resulted in transcription of rsu-1 RNA and the accumulation of p33 Rsu-1 protein. Appearance of the Rsu-1 protein correlated with a reduction in growth rate of the U251-Rsu-1 transfectant. In addition, reduction in anchorage independent growth and phenotypic alteration in U251-Rsu-1 transfectant agar colonies was observed. Two U251-Rsu-1 transfectant cell lines were non tumorigenic when injected subcutaneously into athymic nude mice. These results, in conjunction with the frequent deletions observed in chromosome 10 in glioblastomas, suggest that RSU-1 loss of function may play a role in the progression of this disease. FAU - Tsuda, T AU - Tsuda T AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892-1750, USA. FAU - Marinetti, M R AU - Marinetti MR FAU - Masuelli, L AU - Masuelli L FAU - Cutler, M L AU - Cutler ML LA - eng PT - Journal Article PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (DNA, Complementary) RN - 00BH33GNGH (Cadmium) RN - 9038-94-2 (Metallothionein) SB - IM GS - ras GS - rsp-1 GS - rsu-1 MH - Animals MH - Cadmium/pharmacology MH - Cell Division/*genetics MH - Cell Transformation, Neoplastic MH - Chromosome Mapping MH - Chromosomes, Human, Pair 10/*genetics MH - Cricetinae MH - DNA, Complementary MH - Gene Expression MH - *Genes, Tumor Suppressor/drug effects MH - *Genes, ras MH - Glioblastoma/*genetics/*pathology MH - Humans MH - In Situ Hybridization MH - Metallothionein/genetics MH - Mice MH - Mice, Nude MH - Phenotype MH - Promoter Regions, Genetic MH - Transfection MH - Tumor Cells, Cultured EDAT- 1995/07/20 00:00 MHDA- 1995/07/20 00:01 CRDT- 1995/07/20 00:00 PHST- 1995/07/20 00:00 [pubmed] PHST- 1995/07/20 00:01 [medline] PHST- 1995/07/20 00:00 [entrez] PST - ppublish SO - Oncogene. 1995 Jul 20;11(2):397-403.