17beta-Estradiol induces cyclin D1 gene transcription, p36D1-p34cdk4 complex activation and p105Rb phosphorylation during mitogenic stimulation of G(1)-arrested human breast cancer cells

MCF-7 human breast cancer cells express functional estrogen receptor and grow in response to estrogen stimulation. G(1)-synchronized MCF-7 cells, made quiescent by exposure to the HMG-CoA reductase inhibitor Simvastatin in estrogen-free medium, readily resume cell cycle progression upon stimulation with 17beta-estradiol (E(2)), even under conditions where polypeptide growth factor-triggered signal transduction pathways are inhibited by the continuous presence of Simvastatin in the culture medium. Under these conditions, cyclin D(1) gene transcription is transiently induced within the first 1-9 h of stimulation, as shown by the accumulation of cyclin D(1) mRNA and protein (p36(D(1))) in the cell and by enhanced expression of stably transfected D(1) promoter-luciferase hybrid genes. Estrogen-induced p36(D(1)) associates readily with p32(cdk2) and p34(cdk4), but not with p31(cdk5), which is however abundantly expressed in these cells. Only p36(D(1))-p34(cdk4) complexes are activated by E(2), as detected in cell extracts by immunoprecipitation with anti-D(1) antibodies followed by assessment of phosphotransferase activity toward the retinoblastoma (Rb) gene product and by analysis of p105(Rb) phosphorylation in vivo. An estrogen-responsive regulatory region has been mapped within the first 944 bp upstream of the transcriptional startsite of the human D(1) gene. Sequence analysis of this DNA region reveals that the cis-acting elements responsive to estrogen are likely to be different in this case from the canonical EREs.

Medienart:

Artikel

Erscheinungsjahr:

1996

Erschienen:

1996

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Oncogene - 12(1996), 11 vom: 06. Juni, Seite 2315-24

Sprache:

Englisch

Beteiligte Personen:

Altucci, L [VerfasserIn]
Addeo, R [VerfasserIn]
Cicatiello, L [VerfasserIn]
Dauvois, S [VerfasserIn]
Parker, M G [VerfasserIn]
Truss, M [VerfasserIn]
Beato, M [VerfasserIn]
Sica, V [VerfasserIn]
Bresciani, F [VerfasserIn]
Weisz, A [VerfasserIn]

Themen:

136601-57-5
1CC1JFE158
4TI98Z838E
9007-49-2
9LHU78OQFD
AGG2FN16EV
CDK4 protein, human
Cyclin D1
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases
Cyclins
DNA
Dactinomycin
EC 1.13.12.-
EC 2.7.11.22
Estradiol
Journal Article
Lovastatin
Luciferases
Oncogene Proteins
Proto-Oncogene Proteins
RNA, Messenger
Research Support, Non-U.S. Gov't
Retinoblastoma Protein
Simvastatin

Anmerkungen:

Date Completed 22.07.1996

Date Revised 21.11.2013

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM086238345