Divergent effects of epidermal growth factor and transforming growth factors on a human endometrial carcinoma cell line

Murray Korc, Carol A. Haussler, Nathan S. Trookman

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Epidermal growth factor (EGF), at concentrations ranging from 0.83 to 4.98 nM, markedly inhibited the proliferation of RL95-2 cells that were seeded at low plating densities (4.7 x 103cells/cm2). Under the same incubation conditions, 16.6 pM EGF enhanced cell proliferation. At high plating densities (2.5×104 cells/cm2) 0.83 nM EGF also stimulated cell proliferation. Both the inhibitory and stimulatory effects of EGF were mimicked by transforming growth factor-a (TGF-a). However, the inhibitory action of TGF-a was always greater than that of EGF. Binding studies with 125I-labeled TGF-α indicated that maximal cell surface binding of TGF-α occurred at 15 min, whereas maximal internalization occurred at 45 min. Both cell surface and internalized radioactivity declined sharply thereafter. Analysis of radioactivity released into the incubation medium during pulse-chase experiments indicated that RL95-2 cells extensively degraded both TGF-α and EGF. The lysosomotropic compound methylamine arrested the generation of low-molecular-weight degradation products of EGF, but not of TGF-α. In contrast to EGF and TGF-α, transforming growth factor-β (TGF-β) inhibited the proliferation of RL95-2 cells that were seeded at either low or high plating densities. Further, transforming growth factor-β induced the appearance of large cuboidal cells that were readily distinguished from cells treated with either EGF or TGF-α. These findings point to complex regulatory actions of growth factors on the proliferation of RL95-2 cells and suggest that the processing of TGF-α following EGF receptor activation is distinct from the processing of EGF.

Original languageEnglish (US)
Pages (from-to)4909-4914
Number of pages6
JournalCancer Research
Volume47
Issue number18
StatePublished - Sep 15 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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