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Phorbol ester induced phosphorylation of the estrogen receptor in intact MCF-7 human breast cancer cells

Journal Article · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7186745
; ; ;
Recent studies with a variety of cellular receptors have shown that phorbol ester induced phosphorylation modulates ligand binding and function. In this study the authors present direct evidence that the estrogen receptor in MCF-7 human breast cancer cells is a phosphoprotein whose phosphorylation state can be enhanced specifically by phorbol-12-myristate-13-acetate (PMA). Cells were cultured to 6h in the presence of (/sup 32/P)-orthophosphate. Whole cell extracts were immunoprecipitated with a monoclonal antibody (D58) against the estrogen receptor and subjected to SDS-polyacrylamide electrophoresis. Autoradiography showed a specific band in the region of 60-62 kDa which was significantly increased in preparations from PMA treated cells. Phospho-amino acid analysis demonstrated specific phosphorylation of serine and threonine residues. Cholera toxin or forskolin did not change the phosphorylation state of this protein. In a parallel binding analysis PMA led to a rapid decrease of estrogen binding sites. The estrogen induction of both progesterone receptors and growth in semisolid medium was blocked by PMA, whereas the estrogen induction of the 8kDa protein corresponding to the ps2 gene product and of the 52 kDa protein was not affected. In conclusion, phorbol esters can induce phosphorylation of the estrogen receptor. This process may be associated with the inactivation of certain receptor functions.
Research Organization:
National Institutes of Health, Bethesda, MD
OSTI ID:
7186745
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIGENS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARCINOGENS
CELL CULTURES
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
ELECTROPHORESIS
ESTERS
ESTROGENS
GLANDS
HORMONES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAMMARY GLANDS
MAN
MATERIALS
MEMBRANE PROTEINS
MONOCLONAL ANTIBODIES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHORBOL ESTERS
PHOSPHATES
PHOSPHORUS 32
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PRIMATES
PROTEINS
RADIOISOTOPES
RECEPTORS
STEROID HORMONES
TOXIC MATERIALS
TOXINS
TUMOR CELLS
VERTEBRATES