التفاصيل البيبلوغرافية
| العنوان: |
The tumor suppressor PTEN inhibits EGF-induced TSP-1 and TIMP-1 expression in FTC-133 thyroid carcinoma cells |
| المؤلفون: |
Soula-Rothhut, Mahdhia1, Coissard, Cyrille1, Sartelet, Hervé1, Boudot, Cédric1, Bellon, Georges2, Martiny, Laurent1, Rothhut, Bernard1 bernard.rothhut@univ-reims.fr |
| المصدر: |
Experimental Cell Research. Mar2005, Vol. 304 Issue 1, p187-201. 15p. |
| مصطلحات موضوعية: |
*EPIDERMAL growth factor, *CYTOKINES, *CELL culture, *EXTRACELLULAR matrix proteins |
| مستخلص: |
Abstract: Thrombospondin-1 (TSP-1) is a multidomain extracellular macromolecule that was first identified as natural modulator of angiogenesis and tumor growth. In the present study, we found that epidermal growth factor (EGF) up-regulated TSP-1 expression in FTC-133 (primary tumor) but not in FTC-238 (lung metastasis) thyroid cancer cells. Both EGF and TSP-1 induced expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. In FTC-133 cells, EGF induced proliferation in a TSP-1- and TIMP-1-dependent manner. In addition, we determined that re-expression of the tumor suppressor protein PTEN induced cell death, an effect that correlated with a block of Akt kinase phosphorylation. EGF-induced TSP-1 and TIMP-1 promoter activity and protein expression were inhibited in FTC-133 cells stably expressing wtPTEN but not in cells expressing mutant PTEN. Furthermore, we found that wtPTEN inhibited EGF—but not TSP-1—stimulated FTC-133 cell migration and also inhibited invasion induced by EGF and by TSP-1. Finally, an antibody against TSP-1 reversed EGF-stimulated FTC-133 cell invasion as well as the constitutive invasive potential of FTC-238 cells. Overall, our results suggest that PTEN can function as an important modulator of extracellular matrix proteins in thyroid cancer. Therefore, analyzing differential regulation of TSP-1 by growth factors such as EGF can be helpful in understanding thyroid cancer development. [Copyright &y& Elsevier] |
| قاعدة البيانات: |
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