Differential Binding and Biological Activities of Epidermal Growth Factor and Transforming Growth Factor a in a Human Pancreatic Cancer Cell Line

Murray Korc, Bysani Chandrasekar, Gui N. Shah

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The binding characteristics and biological activities of epidermal growth factor (EGF) and transforming growth factor a (TGF-a) were studied in T3M4 human pancreatic cancer cells. Scatchard analysis of '“I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites: a high-affinity site (K¿= 0.58 HM;25,300 sites/cell) and a low-affinity site (Ka = 7.0 nivi;484,000 sites/cell). At pH 8.5, there was a decrease in the number of high-affinity sites. In contrast, only a single order of high-affinity sites was detected with l25I-TGF-a at either pH 7.4 (#„= 0.57 nivi; 100,200 sites/cell) or pH 8.5 (*„= 0.70 nM; 230,400 sites/cell). The two ligands bound to the same receptor, as determined in cross-linking experiments and in competitive binding assays performed in the presence of an anti-EGF receptor antibody that allows for EGF binding. Phosphoamino acid analysis of the immunoprecipitated EGF receptor indicated that EGF exerted a greater effect than TGF-a on tyrosine phosphorylation of the receptor. EGF and TGF-a also exhibited different potencies with respect to their effects on ¡nositol1,4,5-trisphosphate generation and exerted divergent effects on the kinetics of inositol 1,4,5-trisphosphate formation. These findings point to dissimilar inter actions of EGF and TGF-a with the EGF receptor in T3M.i cells, which may lead to differential activation of signal transduction pathways by these ligands.

Original languageEnglish (US)
Pages (from-to)6243-6249
Number of pages7
JournalCancer Research
Volume51
StatePublished - Dec 1991

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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