ag-556 and Pancreatic-Neoplasms

The pancreas harbors growth factors such as the epidermal growth factor (EGF) family. The physiological and pathophysiological roles of growth factors in normal pancreas remain unsettled. Human pancreatic cancer overexpresses the EGF receptor, and the ligands EGF and transforming growth factor alpha (TGF-alpha). The aim of the present experiments was to study the effect of TGF-alpha in a pancreatic cancer cell line and in normal mouse pancreas.. The LN-36 cell line, established from a pancreatic duct cell adenocarcinoma, was incubated with TGF-alpha or EGF. The effect of an EGF receptor-specific, tyrosine kinase inhibitor (tyrphostin B56) with or without growth factors was also studied. The cell number was measured with the XTT-colorimetric method. TGF-alpha, the tyrphostins A25, B48, and B56, were in separate experiments infused during 1 wk to normal female mice by subcutaneous (sc) minipumps.. The LN-36 cell line responded to TGF-alpha and EGF with increased cell number; +61% with 10(-10) M TGF-alpha and +34% with 10(-9) M EGF. Tyrphostin B56 at a concentration of 10(-5) M reduced the cell number by 76%, but when incubated together with growth factors the reduction was only 44% with TGF-alpha, and 39% with EGF. Infusion of TGF-alpha increased mouse pancreatic wet weight and protein content but was without effect on DNA synthesis, measured as incorporation of tritiated thymidine. Infusion of three different tyrphostins did not influence mice pancreas.. The results support the role of TGF-alpha to maintain growth of pancreatic cancer cells by the EGF receptor. Infusion of TGF-alpha induced hypertrophy in normal mouse pancreas.

Topics: Animals; Cell Count; Dose-Response Relationship, Drug; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Hypertrophy; Mice; Pancreas; Pancreatic Neoplasms; Transforming Growth Factor alpha; Tumor Cells, Cultured; Tyrphostins

Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36.. The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines.. MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56.. MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

Topics: Antibodies; Cell Count; Enzyme Inhibitors; Epidermal Growth Factor; ErbB Receptors; Humans; Insulin-Like Growth Factor I; Pancreatic Neoplasms; Receptor, IGF Type 1; Tumor Cells, Cultured; Tyrphostins