Ganglioside GD1a regulation of caveolin-1 and Stim1 expression in mouse FBJ cells: augmented expression of caveolin-1 and Stim1 in cells with increased GD1a content.
GD1a was previously shown responsible for regulating cell motility, cellular adhesiveness to vitronectin, phosphorylation of c-Met and metastatic ability of mouse FBJ osteosarcoma cells. To determine the particular molecules regulated by GD1a, FBJ cells were assessed for tumor-related gene expression by semi-quantitative RT-PCR. Caveolin-1 and stromal interaction molecule 1 (Stim1) expression in FBJ-S1 cells, rich in GD1a, were found to be 6 and 4 times as much, respectively, than in FBJ-LL cells devoid of GD1a. Enhanced production of caveolin-1 in protein was confirmed by Western blotting. A low-metastatic FBJ-LL cell variant, having high GD1a expression through beta1-4GalNAcT-1 (GM2/GD2 synthase) cDNA transfection (Hyuga S, et al, Int J Cancer 83: 685-91, 1999), showed enhanced production of caveolin-1 and Stim1 in mRNA and protein, compared to mock-transfectant M5. Incubation of FBJ-M5 cells with exogenous GD1a augmented the expression of caveolin-1 in mRNA and protein and Stim1 in mRNA as well. Treatment of FBJ-S1 with fumonisin B1, an inhibitor of N-acylsphinganine synthesis, for 15 days caused the complete depletion of gangliosides and suppressed the expression of caveolin-1 and Stim1. St3gal5 siRNA transfected cells showed decreased expression of caveolin-1 and Stim1 mRNA, as well as St3gal5 mRNA. These findings clearly indicate ganglioside GD1a to be involved in the regulation of the transformation suppressor genes, caveolin-1 and Stim1. Moreover, treatment with GD1a of mouse melanoma B16 cells and human hepatoma HepG2 cells brought about elevated expression of caveolin-1 and Stim1.
Wang
Li
L
Laboratory of Tumor Biology and Glycobiology, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Takaku
Shizuka
S
Wang
Pu
P
Hu
Dan
D
Hyuga
Sumiko
S
Sato
Toshinori
T
Yamagata
Sadako
S
Yamagata
Tatsuya
T
D000818:Animals; D015220:Calcium Channels; D002417:Cattle; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D000071737:Stromal Interaction Molecule 1; D015854:Up-Regulation / Q000502:physiology*
D015220:Calcium Channels; D051242:Caveolin 1; D005732:Gangliosides; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; C021298:ganglioside, GD1a