Document Detail


Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of beta 1,4GalNAc transferase.
MedLine Citation:
PMID:  15178323     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and beta 1,4GalNAc disialyl-Lc(4) (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of beta 1,4GalNAc transferase (beta 1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, beta 1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same beta 1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of beta 1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex.
Authors:
Hiroshi Aoki; Makoto Satoh; Koji Mitsuzuka; Akihiro Ito; Seiichi Saito; Tadao Funato; Mareyuki Endoh; Toshiko Takahashi; Yoichi Arai
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  FEBS letters     Volume:  567     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-04     Completed Date:  2004-07-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  203-8     Citation Subset:  IM    
Affiliation:
Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi Aoba-ku, Sendai 980-8574, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antigens / biosynthesis
Antigens, CD / biosynthesis
Carcinoma, Renal Cell / genetics,  metabolism,  pathology*
Cell Division / genetics
Cell Line, Tumor
Cell Movement / genetics*
G(M2) Ganglioside / biosynthesis
G(M3) Ganglioside / biosynthesis
Gene Expression Regulation, Neoplastic / genetics
Humans
Kidney Neoplasms / genetics,  metabolism,  pathology*
Male
Membrane Glycoproteins / biosynthesis
Middle Aged
N-Acetylgalactosaminyltransferases / biosynthesis,  genetics*
Neoplasm Invasiveness
RNA / genetics,  pharmacology
RNA, Messenger / biosynthesis
RNA, Small Interfering / genetics*
Transfection
Chemical
Reg. No./Substance:
0/Antigens; 0/Antigens, CD; 0/CD9 antigen; 0/G(M3) Ganglioside; 0/Membrane Glycoproteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 19600-01-2/G(M2) Ganglioside; 63231-63-0/RNA; EC 2.4.1.-/N-Acetylgalactosaminyltransferases

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