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Divergent Effects of Epidermal Growth Factor and Transforming Growth Factors on a Human Endometrial Carcinoma Cell Line¹

Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona 85724

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 10³ cells/cm²). Under the same incubation conditions, 16.6 pM EGF enhanced cell proliferation. At high plating densities (2.5 x 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- (TGF-). However, the inhibitory action of TGF- was always greater than that of EGF. Binding studies with ¹²⁵I-labeled TGF- indicated that maximal cell surface binding of TGF- 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- and EGF. The lysosomotropic compound methylamine arrested the generation of low-molecular-weight degradation products of EGF, but not of TGF-. In contrast to EGF and TGF-, transforming growth factor-ß (TGF-ß) inhibited the proliferation of RL95-2 cells that were seeded at either low or high plating densities. Further, transforming growth factor-ß induced the appearance of large cuboidal cells that were readily distinguished from cells treated with either EGF or TGF-. These findings point to complex regulatory actions of growth factors on the proliferation of RL95-2 cells and suggest that the processing of TGF- following EGF receptor activation is distinct from the processing of EGF.

¹ This investigation was supported by USPHS Grant CA-40162 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Endocrine Section, Room 6411, Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724.

Received 1/20/87. Revised 5/13/87. Accepted 6/24/87.

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