PMID- 7629160
OWN - NLM
STAT- MEDLINE
DCOM- 19950907
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 31
DP  - 1995 Aug 4
TI  - Effects of tumor necrosis factor-alpha on antimitogenicity and cell cycle-related 
      proteins in MCF-7 cells.
PG  - 18367-73
AB  - Tumor necrosis factor-alpha (TNF-alpha) demonstrated antimitogenic activity in 
      MCF-7 cells (estrogen receptor-positive human breast cancer cells) in a dose- and 
      time-dependent manner (EC-50 of 2.5 ng/ml). This antimitogenic effect of 
      TNF-alpha was accompanied by a decreased number of cells in S phase in a dose- 
      and time-dependent manner. Based on growth arrest experiments using aphidicolin, 
      it is apparent that TNF-alpha acted in early G1 phase. It did not show 
      antimitogenic effects once cells reentered the S phase based on [3H]thymidine 
      incorporation into DNA and cell cycle analysis. Specificity of TNF-alpha was 
      established by using monoclonal anti-human TNF-alpha antibody. On the basis of 
      Western immunoblot analysis of Rb, p53 and cell cycle inhibitory protein (Cip1) 
      (p21) proteins, TNF-alpha decreased Rb protein expression in a dose- and 
      time-dependent manner whereas it increased the expression level of tumor 
      suppressor p53 protein. TNF-alpha also increased the expression level of Cip1 
      (p21) protein in a dose-dependent manner. This induction of Cip1 (p21) protein 
      was preceded by the induction of p53 protein in MCF-7 cells. Cip1 (p21) protein 
      associated with cyclin D was also increased. Tumor suppressor Rb protein 
      expression was increased during G1 to S phase progression. Cyclin D protein 
      expression levels were not changed in response to TNF-alpha treatment, although 
      serine/threonine kinase inhibitors such as H7 and the protein kinase C inhibitor 
      staurosporine decreased cyclin D expression levels in MCF-7 cells. Based on 
      experiments with staurosporine, it appears that TNF-alpha does not utilize a 
      protein kinase C pathway in MCF-7 cells. Other cell cycle-related proteins such 
      as Cdk2, Cdc2, and Cdk4 did not show any change in response to TNF-alpha. 
      TNF-alpha did not affect complexes between cyclin D and Cdk2, Cdk4, and Rb 
      proteins in MCF-7 cells. Taken together these results suggest that Rb, p53, and 
      Cip1 (p21) proteins mediate TNF-alpha antimitogenic activity, and TNF-alpha 
      induces growth arrest in the G1 phase in MCF-7 cells.
FAU - Jeoung, D I
AU  - Jeoung DI
AD  - Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
FAU - Tang, B
AU  - Tang B
FAU - Sonenberg, M
AU  - Sonenberg M
LA  - eng
GR  - CA09512/CA/NCI NIH HHS/United States
GR  - DK 41931/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Breast Neoplasms/*metabolism
MH  - Cell Cycle/*drug effects
MH  - Cell Cycle Proteins/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Kinetics
MH  - Phosphorylation
MH  - Protein Binding
MH  - Retinoblastoma Protein/metabolism
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/immunology/*pharmacology
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 1995/08/04 00:00
MHDA- 1995/08/04 00:01
CRDT- 1995/08/04 00:00
PHST- 1995/08/04 00:00 [pubmed]
PHST- 1995/08/04 00:01 [medline]
PHST- 1995/08/04 00:00 [entrez]
AID - S0021-9258(17)46316-2 [pii]
AID - 10.1074/jbc.270.31.18367 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Aug 4;270(31):18367-73. doi: 10.1074/jbc.270.31.18367.