Ganglioside GD1a suppression of NOS2 expression via ERK1 pathway in mouse osteosarcoma FBJ cells.

Abstract

Inducible nitric oxide synthase (NOS2) is over-expressed in a number of tumors and implicated in tumor growth and metastasis. Murine FBJ osteosarcoma-derived FBJ-S1 cells are poorly metastatic and express the ganglioside GD1a, whereas highly metastatic FBJ-LL cells only slightly express this ganglioside. The present study demonstrates that NOS2 is more highly expressed in FBJ-LL cells compared to FBJ-S1 cells. By manipulating GM2/GD2 synthase expression or adding exogenous GD1a, GD1a inversely regulated NOS2 at the transcriptional level. GT1b suppressed NOS2 to the same extent as GD1a. Silencing NOS2 inhibited proliferation, migration, and anchorage-independent growth of FBJ-LL cells, suggesting that the metastatic properties of FBJ-LL cells are associated with NOS2. MEK1/2 inhibitor (U0126) increased NOS2 expression, whereas GD1a treatment decreased it. Co-treating the cells with GD1a and U0126 blocked the inhibition of NOS2 expression, suggesting that the GD1a signal is mediated by ERK1/2. NOS2 expression increased when ERK1, but not ERK2, was silenced, and GD1a did not suppress NOS2 expression in cells treated with another MEK1/2 inhibitor PD98059, suggesting that ERK1 phosphorylation is indispensable for the GD1a signal suppressing NOS2.

• Authors: Ting Cao, Tianyi Zhang, Li Wang, Lan Zhang, Tomoko Adachi, Toshinori Sato, Sadako Yamagata, Tatsuya Yamagata
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 110 Issue 5 Pg. 1165-74 (Aug 01 2010) ISSN: 1097-4644 [Electronic] United States
• PMID: 20589721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published 2010 Wiley-Liss, Inc.

Chemical References

• Butadienes
• Enzyme Inhibitors
• Flavonoids
• Gangliosides
• Nitriles
• U 0126
• ganglioside, GD1a
• trisialoganglioside GT1
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Mitogen-Activated Protein Kinase 3
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Blotting, Western
• Butadienes (pharmacology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Enzyme Inhibitors (pharmacology)
• Flavonoids (pharmacology)
• Gangliosides (metabolism, pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Nitriles (pharmacology)
• Osteosarcoma (genetics, metabolism, pathology)
• Phosphorylation (drug effects)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction