PMID- 11373057 OWN - NLM STAT- MEDLINE DCOM- 20010927 LR - 20181130 IS - 0169-4197 (Print) IS - 0169-4197 (Linking) VI - 28 IP - 3 DP - 2000 Dec TI - Transforming growth factor alpha (TGF-alpha) increases cell number in a human pancreatic cancer cell line but not in normal mouse pancreas. PG - 199-205 AB - BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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. FAU - Kullenberg, B AU - Kullenberg B AD - Department of Surgery, Lund University, Sweden. FAU - Jansen, C AU - Jansen C FAU - Fredang, N AU - Fredang N FAU - Ohlsson, B AU - Ohlsson B FAU - Axelson, J AU - Axelson J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Pancreatol JT - International journal of pancreatology : official journal of the International Association of Pancreatology JID - 8703511 RN - 0 (Transforming Growth Factor alpha) RN - 0 (Tyrphostins) RN - 149092-35-3 (AG 556) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Cell Count MH - Dose-Response Relationship, Drug MH - Epidermal Growth Factor/pharmacology MH - ErbB Receptors/physiology MH - Female MH - Humans MH - Hypertrophy MH - Mice MH - Pancreas/*drug effects/pathology MH - Pancreatic Neoplasms/*pathology MH - Transforming Growth Factor alpha/*pharmacology MH - Tumor Cells, Cultured MH - Tyrphostins/pharmacology EDAT- 2001/05/25 10:00 MHDA- 2001/09/28 10:01 CRDT- 2001/05/25 10:00 PHST- 2001/05/25 10:00 [pubmed] PHST- 2001/09/28 10:01 [medline] PHST- 2001/05/25 10:00 [entrez] AID - 10.1385/IJGC:28:3:199 [doi] PST - ppublish SO - Int J Pancreatol. 2000 Dec;28(3):199-205. doi: 10.1385/IJGC:28:3:199.