Human Pancreatic Cancer AsPC-1 Cells Research Articles

Activation of PPARγ increases PTEN expression in pancreatic cancer cells

The PI3K pathway contributes to the invasive properties and apoptosis resistance that epitomize pancreatic cancers. PPARγ is a ligand-activated transcription factor with anti-inflammatory and anti-tumor effects; the mechanisms of tumor suppression are unknown. The purpose of this study was to examine whether activation of PPARγ can increase the expression of the tumor suppressor PTEN and inhibit PI3K activity. AsPC-1 human pancreatic cancer cells, transfected with a PPRE-luciferase construct, demonstrated increased luminescence following treatment with PPARγ ligands, indicating the presence of functional PPARγ protein. The selective PPARγ ligand rosiglitazone increased PTEN expression in AsPC-1 cells; concurrent treatment with GW9662, which inhibits PPARγ activation, prevented the increase in PTEN protein levels. Levels of phosphorylated Akt decreased as PTEN levels increased, indicating inhibition of PI3K activity. Taken together, our results suggest that activation of PPARγ may represent a novel approach for the treatment of pancreatic cancer by increasing PTEN levels and inhibiting PI3K activity.

Hepatocyte growth factor stimulates cell growth and enhances the expression of transforming growth factor alpha mRNA in AsPC-1 human pancreatic cancer cells.

We investigated the effects of hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF alpha) on cell growth in four human pancreatic cancer cell lines. Changes in the expression of mRNAs of HGF, c-met, TGF alpha, and epidermal growth factor receptor (EGFR) by treatment with HGF and TGF alpha were observed. Cell growth with growth factors was assessed with the MTT assay and compared with basal growth without growth factors. Although HGF stimulated cell growth in AsPC-1, COLO-357, and T3M4 cells, Panc-1 cells showed no response to HGF. TGF alpha stimulated the growth of all the above cells. The expression of c-met mRNA under nonstimulated conditions was detected with Northern blotting in all cells. Treatment with HGF slightly enhanced the expression of c-met mRNA only in COLO-357 cells. The intensity of EGFR expression was consistent, and HGF mRNA was not detected during induction experiments in any cell type. Concomitant treatment with HGF and TGF alpha exerted an effect that was additive or less on the growth of all cells. Expression of TGF alpha was enhanced by HGF treatment only in AsPC-1 cells. These results suggested that HGF and TGF alpha stimulated cell growth through a final common pathway of signal transduction.