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

Toshitaka Tsuda, Maria Rita Marinetti, Laura Masuelli, Mary Cutler

Research output: Contribution to journalArticle

Abstract

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 Une 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.

Original languageEnglish (US)
Pages (from-to)396-403
Number of pages8
JournalOncogene
Volume11
Issue number2
StatePublished - Jul 20 1995
Externally publishedYes

Fingerprint

Glioblastoma
Cell Line
Chromosomes, Human, Pair 10
Growth
Nude Mice
Proteins
RNA
Hybrid Cells
Metallothionein
Tumor Cell Line
Fluorescence In Situ Hybridization
Adenylyl Cyclases
Agar
Transfection
Disease Progression
Clone Cells
Yeasts
DNA
Genes

Keywords

  • Glioblastoma, tumor suppressor
  • RSU-1

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

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. / Tsuda, Toshitaka; Marinetti, Maria Rita; Masuelli, Laura; Cutler, Mary.

In: Oncogene, Vol. 11, No. 2, 20.07.1995, p. 396-403.

Research output: Contribution to journalArticle

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