| Autor: |
Tennis MA; University of Colorado at Denver and Health Sciences Center, 12700 East 19th Avenue, Box C272, RC2 9th Floor, Aurora, CO 80045, USA. Meredith.tennis@ucdenver.edu, Van Scoyk MM, Freeman SV, Vandervest KM, Nemenoff RA, Winn RA |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular cancer research : MCR [Mol Cancer Res] 2010 Jun; Vol. 8 (6), pp. 833-43. Date of Electronic Publication: 2010 May 25. |
| DOI: |
10.1158/1541-7786.MCR-09-0400 |
| Abstrakt: |
Sprouty proteins are potent receptor tyrosine kinase inhibitors that antagonize growth factor signaling and are involved in lung development. However, little is known about the regulation or targets of Sprouty-4 (Spry4) in lung cancer. Our study aimed to determine the role of Spry4 in non-small cell lung cancer (NSCLC). We found that Spry4 mRNA expression was decreased in NSCLC cell lines and in dysplastic lung cell lines compared with a nontransformed cell line, suggesting that Spry4 has tumor-suppressing activity. When Spry4 was stably transfected into H157 and H2122 NSCLC cell lines, decreased migration and invasion were observed. Matrix metalloproteinase-9 activity was decreased, and the expression of matrix metalloproteinase inhibitors TIMP1 and CD82 were increased. Stable expression of Spry4 led to reduced cell growth and reduced anchorage-independent growth in NSCLC cell lines, along with upregulation of tumor suppressors p53 and p21. Changes in epithelial and mesenchymal markers indicated that Spry4 expression induces a reversal of the epithelial to mesenchymal transition characteristic of tumor cells. Treatment of a nontransformed lung epithelial cell line with short hairpin RNA to Spry4 led to the decreased expression of epithelial markers and increased cell growth, supporting the concept of Spry4 acting as a tumor suppressor. We showed that the activity of the Spry4 promoter is increased by Wnt7A/Fzd9 signaling through peroxisome proliferator-activated receptor gamma. These data present previously undescribed targets of Spry4 and suggest that Spry4 is a downstream target of Wnt7A/Fzd 9 signaling. Spry4 may have efficacy in the treatment of NSCLC. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
