Exp Mol Med.  2009 Feb;41(2):94-101. 10.3858/emm.2009.41.2.012.

STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

• Choi HJ
• Lee JH
• Park SY
• Cho JH
• Han JS

• KMID: 1109432
• DOI: http://doi.org/10.3858/emm.2009.41.2.012

Abstract

Phosphatidic acid (PA), the product of a PLD-mediated reaction, is a lipid second messenger that participates in various intracellular signaling events and is known to regulate a growing list of signaling proteins. We found that Bcl-2 was upregulated by PA treatment in HeLa cells. However, how PA upregulates Bcl-2 expression has not yet been studied. In this study, we tried to discover the mechanisms of Bcl-2 up-regulation by PA treatment in HeLa cells. Treatment with PA resulted in significantly increased expression of Bcl-2 in HeLa cells. Moreover, PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of PLA2, but not by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Treatment of 1,2-dipalmitoryl-sn-glycero-3-phosphate (DPPA) also increased Bcl-2 expression. These results indicate that Bcl-2 expression is mediated by lysophosphatidic acid (LPA), not by arachidonic acid (AA). Thereafter, we used MEK1/2 inhibitor, PD98059 to investigate the relationship between ERK1/2 MAPK and PA-induced Bcl-2 expression. PA-induced Bcl-2 expression was decreased when ERK1/2 was inhibited by PD98059. The transcription factor such as STAT3 which is controlled by ERK1/2 MAPK was increased along with Bcl-2 expression when the cells were treated with PA. Furthermore, STAT3 siRNA treatments inhibited PA-induced Bcl-2 expression, suggesting that STAT3 (Ser727) is involved in PA-induced Bcl-2 expression. Taken together, these findings indicate that PA acts as an important mediator for increasing Bcl-2 expression through STAT3 (Ser727) activation via the ERK1/2 MAPK pathway.

Keyword

extracellular signal-regulated MAP kinases; phosphatidic acids; phospholipases A2; proto-oncogene proteins c-bcl-2; STAT3 transcription factor

MeSH Terms

Enzyme Inhibitors/pharmacology
Gene Expression Regulation, Neoplastic
Hela Cells
Humans
Mitogen-Activated Protein Kinase Kinases/genetics/metabolism
Phosphatidic Acids/*genetics/metabolism
Propranolol/pharmacology
Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism
Quinacrine/pharmacology
RNA, Small Interfering/genetics
STAT3 Transcription Factor/*genetics/metabolism