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Differential induction of growth arrest inducible genes by selenium compounds
Abstract:
The effects of two types of selenium compounds on the expression levels of growth arrest and DNA damage-inducible (gadd) genes and on selected cell death genes were examined in mouse mammary MOD cells to test the hypothesis that the diversity of selenium-induced cellular responses to these compounds could be distinguished by unique gene expression patterns. Whereas the expression patterns of known cell death-related genes (bcl-2 and bax) were not informative with respect to the cellular response patterns upon exposure to selenium compounds, time-dependent and selenium species-specific induction patterns were observed for gadd34, gadd45 and gadd153 genes. It was also observed that the MOD cells expressed a truncated p53 transcript but no detectable immunoreactive P53 protein, indicating a null p53 phenotype. The fact that selenium compounds induced growth arrest and death of these cells and that these compounds induced specific patterns of expression of gadd genes indicates that these genes may mediate some selenium-induced cellular responses. The findings further imply that selenium compounds may be effective chemopreventive agents for human breast carcinogenesis, in which p53 mutations are frequent.
Insights
Selenium compounds induce specific gene expression patterns in mouse mammary cells, suggesting their potential as chemopreventive agents for breast cancer by mediating growth arrest and cell death.
Area of Science:
- Molecular Biology
- Cancer Research
- Toxicology
Background:
- Selenium compounds exhibit diverse cellular effects.
- Understanding selenium's impact on gene expression is crucial for its application in cancer chemoprevention.
- Mouse mammary MOD cells provide a model for studying cellular responses to xenobiotics.
Purpose of the Study:
- To investigate the gene expression patterns induced by different selenium compounds in mouse mammary MOD cells.
- To test if unique gene expression profiles differentiate cellular responses to various selenium compounds.
- To explore the role of growth arrest and DNA damage-inducible (GADD) genes in selenium-mediated cellular effects.
Main Methods:
- Exposure of mouse mammary MOD cells to two types of selenium compounds.
- Analysis of gene expression levels for GADD genes (gadd34, gadd45, gadd153) and cell death genes (bcl-2, bax).
- Assessment of p53 status, including transcript and protein expression.
Main Results:
- Specific, time-dependent, and selenium species-specific induction patterns were observed for gadd34, gadd45, and gadd153 genes.
- Expression patterns of bcl-2 and bax genes were not informative regarding cellular responses to selenium.
- MOD cells exhibited a null p53 phenotype due to a truncated p53 transcript and absence of P53 protein.
- Selenium compounds induced cell growth arrest and death, mediated by specific GADD gene expression patterns.
Conclusions:
- Specific GADD gene induction patterns can distinguish cellular responses to different selenium compounds.
- GADD genes likely mediate some selenium-induced cellular responses, including growth arrest and cell death.
- Selenium compounds show promise as chemopreventive agents against human breast carcinogenesis, particularly in cases with frequent p53 mutations.