Effects of tumor necrosis factor-α on antimitogenicity and cell cycle-related proteins in MCF-7 cells Journal Article
| Authors: | Jeoung, D. I.; Tang, B.; Sonenberg, M. |
| Article Title: | Effects of tumor necrosis factor-α on antimitogenicity and cell cycle-related proteins in MCF-7 cells |
| Abstract: | Tumor necrosis factor-α (TNF-α) 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-α 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-α 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-α was established by using monoclonal anti-human TNF-α antibody. On the basis of Western immunoblot analysis of Rb, p53 and cell cycle inhibitory protein (Cip1) (p21) proteins, TNF-α decreased Rb protein expression in a dose- and time-dependent manner whereas it increased the expression level of tumor suppressor p53 protein. TNF-α 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-α 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-α 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-α. TNF-α 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-α antimitogenic activity, and TNF-α induces growth arrest in the G1 phase in MCF-7 cells. |
| Keywords: | signal transduction; protein phosphorylation; human cell; cell cycle proteins; cell cycle; cell cycle s phase; enzyme inhibition; breast cancer; cell growth; protein binding; drug effect; dose-response relationship, drug; tumor cells, cultured; enzyme activity; breast neoplasms; phosphorylation; protein p53; tumor suppressor gene; gene expression regulation, neoplastic; tumor necrosis factor alpha; kinetics; cancer cell; estrogen receptor; cyclins; retinoblastoma protein; pleiotropy; tumor necrosis factor; growth inhibition; mitogenicity; human; female; priority journal; article; support, u.s. gov't, p.h.s. |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 270 |
| Issue: | 31 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1995-08-04 |
| Start Page: | 18367 |
| End Page: | 18373 |
| Language: | English |
| DOI: | 10.1074/jbc.270.31.18367 |
| PUBMED: | 7629160 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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