Differential binding and biological activities of epidermal growth factor and transforming growth factor α in a human pancreatic cancer cell line

Murray Korc, Bysani Chandrasekar, Gul N. Shah

Research output: Contribution to journalArticle

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Abstract

The binding characteristics and biological activities of epidermal growth factor (EGF) and transforming growth factor α (TGF-α) were studied in T3M4 human pancreatic cancer cells. Scatchard analysis of 125I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites: a high-affinity site (Kd = 0.58 nM; 25,300 sites/cell) and a low-affinity site (Kd = 7.0 nM; 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 125I-TGF-α at either pH 7.4 (Kd = 0.57 nM; 100,200 sites/cell) or pH 8.5 (Kd = 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-α on tyrosine phosphorylation of the receptor. EGF and TGF-α also exhibited different potencies with respect to their effects on inositol 1,4,5-trisphosphate generation and exerted divergent effects on the kinetics of inositol 1,4,5-trisphosphate formation. These findings point to dissimilar interactions of EGF and TGF-α with the EGF receptor in T3M4 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
Issue number23
StatePublished - Dec 1 1991
Externally publishedYes

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Transforming Growth Factors
Pancreatic Neoplasms
Epidermal Growth Factor
Cell Line
Epidermal Growth Factor Receptor
Inositol 1,4,5-Trisphosphate
Phosphoamino Acids
Ligands
Competitive Binding
Signal Transduction
Binding Sites
Phosphorylation
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differential binding and biological activities of epidermal growth factor and transforming growth factor α in a human pancreatic cancer cell line. / Korc, Murray; Chandrasekar, Bysani; Shah, Gul N.

In: Cancer Research, Vol. 51, No. 23, 01.12.1991, p. 6243-6249.

Research output: Contribution to journalArticle

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