%0 Journal Article
%T JNK suppression is essential for 17¦Â-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells
%A Hsi-Hsien Hsu
%A Wei-Syun Hu
%A Yueh-Min Lin
%A Wei-Wen Kuo
%A Li-Mien Chen
%A Wei-Kung Chen
%A Jin-Ming Hwang
%A Fuu-Jen Tsai
%A Chung-Jung Liu
%A Chih-Yang Huang
%J Journal of Biomedical Science
%D 2011
%I BioMed Central
%R 10.1186/1423-0127-18-61
%X We analyzed the protein expression of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human LoVo cells. 17¦Â-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NF¦ÊB inhibitor) and ICI 182 780 were further used to explore the inhibitory effects of 17¦Â-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups.Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17¦Â-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells.Collectively, these results suggest that 17¦Â-estradiol treatment significantly inhibits PGE2-induced motility of human LoVo colon cancer cells.Colorectal carcinoma (CRC) is one of the most prevalent cancers world-wide [1], and is the secondary leading cause of cancer-related mortality in the developed countries [2]. Colon cancer accounts for more than 130,000 new cases per year [3] and causes more than 56,000 deaths per year in United States [4] des
%U http://www.jbiomedsci.com/content/18/1/61