Premium
Phosphorylation and estradiol binding of estrogen receptor in hormone‐dependent and hormone‐independent GR mouse mammary tumors
Author(s) -
Migliaccio Antimo,
Pagano Michele,
de Goeij Cornelis C. J.,
Domenico Marina Di,
Castoria Gabriella,
Sluyser Mels,
Auricchio Ferdinando
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510512
Subject(s) - phosphorylation , medicine , estrogen , endocrinology , dephosphorylation , hormone receptor , estrogen receptor , biology , cytosol , receptor , hormone , phosphatase , biochemistry , enzyme , cancer , breast cancer
The effect of phosphorylation on the hormone‐binding capacity of the estrogen receptor (ER) was investigated in hormone‐dependent (HD) and hormone‐independent (HI) mammary carcinomas of GR mice. Tumor cytosols were incubated with ATP under conditions previously used to study the tyrosine kinase which confers hormone binding to phosphatase‐treated or in vitro ‐synthesized ER. The ATP‐dependent increases in hormone‐binding capacity of 8 out of 20 HI tumors ranged from values of 23 to 124 fmol/mg cytosol protein. The enhancement by ATP of hormone binding to ER was significantly less marked in HD and HR tumors than in HI tumors. In only 3 out of 13 HD and HR tumors was an increase ranging from 15 to 20 fmol/mg protein detected. Analysis by Scatchard plot of estradiol binding to ER showed that cytosol incubation of HI tumors with ATP markedly increased the hormone binding without any change in affinity. The data suggest that ER of HI tumors is less phosphorylated in vivo than the ER of HD/HR tumors, so that the receptor of HI tumors is more susceptible to γ 32 P‐ATP phosphorylation and ATP‐induced hormone binding in vitro . Western blot of ER with antiphosphotyrosine antibody showed that, in HI tumors, the large ATP‐induced increase in hormone binding to ER was associated with phosphorylation on tyrosine of the receptor itself. Our findings indicate that the process of activation‐inactivation of binding through tyrosine‐phosphorylation/ phosphotyrosine‐dephosphorylation of ER observed in estrogen target tissues is altered in some HI mammary tumors. © 1992 Wifey‐Liss, Inc.