Modulation of epidermal growth factor receptor binding and action by N-acetyl-TGF alpha (34-43) methyl ester.
Controversial data have been reported concerning the ability of N-acetyl-TGF alpha (34-43) methyl ester (TGF alpha A) to antagonize the mitogenic effect or the receptor binding of TGF alpha and EGF. We reinvestigated the effect of TGF alpha A on various EGF-sensitive cell lines and in reaggregate and monolayer cell cultures of rat anterior pituitary. In reaggregate pituitary cell cultures, EGF dose-dependently increased [3H]thymidine ([3H]T) incorporation in lactotrophs and decreased [3H]T incorporation in somatotrophs. TGF alpha A (5 microM) completely blocked the effect of 0.1 nM EGF on both lactotrophs and somatotrophs. It had no intrinsic effect on its own. However, depending on the batch of [125I]EGF used, a dose of 5-10 microM TGF alpha A did not or only partially inhibited the binding of 3 x 10(-10) M [125I]EGF to pituitary monolayer cell cultures. In the EGF-sensitive cell lines A-431, BS-C-1, NRK-52E, and pituitary GH3 cells, none of the EGF effects were antagonized by TGF alpha A. On the contrary, the EGF effect was slightly augmented in A-431 cells. In GH3 cells TGF alpha A was clearly mitogenic on its own. It is concluded that, although TGF alpha A negatively interacts with EGF action and binding in normal pituitary, this is most likely not due to a direct competition with the binding of EGF.
Andries
M
M
Department of Pharmacology, Katholieke Universiteit Leuven, Belgium.
Tilemans
D
D
Denef
C
C
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008934:Mitogens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D008934:Mitogens; D010446:Peptide Fragments; C090017:TGF-alpha (34-43) methyl ester, N-acetyl-; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors