Regulation of transforming growth factor-beta type II receptor expression in human breast cancer MCF-7 cells by vitamin D3 and its analogues

In view of the tumor suppressor role of the transforming growth factor-beta (TGFbeta) type II receptor (RII), the identification and characterization of agents that can induce the expression of this receptor are of potential importance to the development of chemoprevention approaches as well as trea...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-03, Vol.273 (13), p.7749
Main Authors: Wu, G, Fan, R S, Li, W, Srinivas, V, Brattain, M G
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Calcitriol - analogs & derivatives
Calcitriol - pharmacology
Cholecalciferol - analogs & derivatives
Cholecalciferol - pharmacology
DNA Replication - drug effects
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Kinetics
Protein-Serine-Threonine Kinases - metabolism
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta - biosynthesis
Receptors, Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta - genetics
Tumor Cells, Cultured
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Summary:In view of the tumor suppressor role of the transforming growth factor-beta (TGFbeta) type II receptor (RII), the identification and characterization of agents that can induce the expression of this receptor are of potential importance to the development of chemoprevention approaches as well as treatment of cancer. To date, the identification of exogenous agents that control RII expression has been rare. We demonstrated that proliferation of MCF-7 early passage cells (MCF-7 E), which express RII and are sensitive to TGFbeta growth inhibition activity, was significantly inhibited by vitamin D3 and its analogue EB1089. In contrast, proliferation of MCF-7 late passage cells (MCF-7 L), which have lost cell surface RII and are resistant to TGFbeta, was not affected by these two compounds. TGFbeta-neutralizing antibody was able to block the inhibitory effect on MCF-7 E cells by these compounds, indicating that treatment induced autocrine-negative TGFbeta activity. An RNase protection assay showed approximately a 3-fold induction of the RII mRNA, while a receptor cross-linking assay revealed a 3-4-fold induction of the RII protein. In contrast, there was no change in either RII mRNA or protein in the MCF-7 L cells.
ISSN:0021-9258
DOI:10.1074/jbc.273.13.7749