Differential induction of growth arrest inducible genes by selenium compounds.
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.
Kaeck
M
M
AMC Cancer Research Center, Denver, CO 80214, U.S.A.
Lu
J
J
Strange
R
R
Ip
C
C
Ganther
H E
HE
Thompson
H J
HJ
D000818:Animals; D000943:Antigens, Differentiation; D015152:Blotting, Northern; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D002452:Cell Count; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D054645:Protein Phosphatase 1; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018036:Selenium Compounds / Q000494:pharmacology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D054645:Protein Phosphatase 1; D011506:Proteins; D012333:RNA, Messenger; D018036:Selenium Compounds; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C497250:Ddit3 protein, mouse; C513256:Ppp1r15a protein, mouse