Format

Send to

Choose Destination
Biochem J. 2000 Jun 1;348 Pt 2:257-61.

Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells.

Author information

1
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, 29071 Málaga, Spain.

Abstract

Phosphate-activated glutaminase has a critical role in tumours and rapidly dividing cells and its activity is correlated with malignancy. Ehrlich ascites tumour cells transfected with the pcDNA3 vector containing an antisense segment (0.28 kb) of rat kidney glutaminase showed impairment in the growth rate and plating efficiency, as well as a shortage in the glutaminase protein and activity. The C-terminal segment used is well conserved in all glutaminase sequences known. The transfected cells, named 0.28AS-2, displayed remarkable changes in their morphology compared with the parental cell line. The 0.28AS-2 cells also lost their tumourigenic capacity in vivo. Control mice developed an ascitic tumour, with a lifespan of 16+/-1 days, when inoculated with 10(7) cells/mouse; on the contrary, animals inoculated with transfected cells up to 2.5 times the cell numbers of control mice did not develop tumours and behaved as healthy animals. The ability to revert the transformed phenotype of antisense-transfected cells confirms the relevance of glutaminase in the transformation process and could provide new ways for the study of gene therapy.

PMID:
10816417
PMCID:
PMC1221061
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center