|
KMID : 0620920080400060607
|
|
Experimental & Molecular Medicine
2008 Volume.40 No. 6 p.607 ~ p.616
|
|
|
Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells
|
|
Jeong Kang-Jin
Choi Wahn-Soo
Kim Yong-Kee
Han Jeung-Whan
Park Soon-Young
Seo Ji-Hye
Lee Kyung-Bok
Kang Jae-Ku
Park Chang-Gyo
Lee Hoi-Young
|
|
|
Abstract
|
|
|
|
Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.
|
|
|
KEYWORD
|
|
|
cell movement, cyclooxygenase-2, lysophosphatidic acid, ovarian neoplasms, proto-oncogene proteins pp60 (c-src), receptors, lysophosphatidic acid
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|