PMID- 10228164
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 9
DP  - 1999 May 4
TI  - Non-transcriptional action of oestradiol and progestin triggers DNA synthesis.
PG  - 2500-10
AB  - The recent findings that oestradiol and progestins activate the Src/Ras/Erks
      signalling pathway raise the question of the role of this stimulation.
      Microinjection experiments of human mammary cancer-derived cells (MCF-7 and T47D)
      with cDNA of catalytically inactive Src or anti-Ras antibody prove that Src and
      Ras are required for oestradiol and progestin-dependent progression of cells
      through the cell cycle. The antitumoral ansamycin antibiotic, geldanamycin,
      disrupts the steroid-induced Ras-Raf-1 association and prevents Raf-1 activation 
      and steroid-induced DNA synthesis. Furthermore, the selective MEK 1 inhibitor, PD
      98059, inhibits oestradiol and progestin stimulation of Erk-2 and the
      steroid-dependent S-phase entry. The MDA-MB231 cells, which do not express
      oestradiol receptor, fail to respond to oestradiol in terms of Erk-2 activation
      and S-phase entry. Fibroblasts are made equally oestradiol-responsive in terms of
      DNA synthesis by transient transfection with either the wild-type or the
      transcriptionally inactive mutant oestradiol receptor (HE241G). Co-transfection
      of catalytically inactive Src as well as treatment with PD98059 inhibit the
      oestradiol-dependent S-phase entry of fibroblasts expressing either the wild-type
      oestrogen receptor or its transcriptionally inactive mutant. The data presented
      support the view that non-transcriptional action of the two steroids plays a
      major role in cell cycle progression.
FAU - Castoria, G
AU  - Castoria G
AD  - Istituto di Patologia Generale e Oncologia, Facolta di Medicina e Chirurgia, II
      Universita di Napoli, Largo S.Aniello a Caponapoli, 2, 80138 Napoli, Italy.
FAU - Barone, M V
AU  - Barone MV
FAU - Di Domenico, M
AU  - Di Domenico M
FAU - Bilancio, A
AU  - Bilancio A
FAU - Ametrano, D
AU  - Ametrano D
FAU - Migliaccio, A
AU  - Migliaccio A
FAU - Auricchio, F
AU  - Auricchio F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Benzoquinones)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Flavonoids)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Progestins)
RN  - 0 (Quinones)
RN  - 0 (Receptors, Estradiol)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - Z3K3VJ16KU (geldanamycin)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Benzoquinones
MH  - Breast Neoplasms/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Division
MH  - DNA, Neoplasm/biosynthesis
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Flavonoids/pharmacology
MH  - Genes, ras
MH  - Genes, src
MH  - Humans
MH  - Lactams, Macrocyclic
MH  - MAP Kinase Kinase 1
MH  - Mice
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Progestins/*pharmacology
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Quinones/pharmacology
MH  - Receptors, Estradiol/metabolism
MH  - S Phase
MH  - Signal Transduction
MH  - Transcription, Genetic
MH  - ras Proteins/metabolism
PMC - PMC1171332
EDAT- 1999/05/06 00:00
MHDA- 1999/05/06 00:01
CRDT- 1999/05/06 00:00
PHST- 1999/05/06 00:00 [pubmed]
PHST- 1999/05/06 00:01 [medline]
PHST- 1999/05/06 00:00 [entrez]
AID - 10.1093/emboj/18.9.2500 [doi]
PST - ppublish
SO  - EMBO J. 1999 May 4;18(9):2500-10. doi: 10.1093/emboj/18.9.2500.