Modulation of mts1 expression in mouse and human normal and tumor cells.
The mts1 gene, encoding small Ca(2+)-binding protein of the S100-family, is considered as a gene whose activity correlates with the manifestation of a metastatic phenotype of tumor cells. It was shown before that the mts1 is expressed not only in metastatic tumor cells but also in some normal tissues, namely in so-called "lymphoid" organs: spleen, thymus, bone marrow. In this work we analyzed in more detail the expression of mts1 in human and mouse hematopoietic cells and cell lines. A high level of mts1 RNA was observed in T-lymphocytes, neutrophils, monocytes/macrophages and in corresponding cell lines. Controversially, the mts1 gene was silent in B-lymphocytes as well as in myeloma and erythroleukemia cell lines. The possibility of modulating the mts1 gene expression by the action of different agents was demonstrated. Mitogens, such as lipopolysaccharides (LPS), interferon (IFN gamma), and concanavalin A (Con A), modulate the level of the mts1 gene expression in hematopoietic cells differently. Calcium ionophore, A23187, can also be regarded as a modulator of the mts1 gene expression, since its addition to the cells results in a substantial decrease of the mts1 RNA level. It was shown that the mts1 RNA's half-life is relatively long, more than 24 h. We therefore believe that calcium ionophore can activate some ribonucleases which degrade the mts1 RNA. Cycloheximide prevents the effect of A23187 and stabilizes the mts1 RNA, probably by blocking the synthesis of these nucleases. Thus, the obtained data indicate that the agents which are capable of changing the physiological status of the cells also modulate the mts1 gene expression.
Grigorian
M
M
Danish Cancer Society, Department of Molecular Cancer Biology, Copenhagen.
Tulchinsky
E
E
Burrone
O
O
Tarabykina
S
S
Georgiev
G
G
Lukanidin
E
E
D000818:Animals; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002460:Cell Line; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D008934:Mitogens; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C077591:S100A4 protein, human; D003609:Dactinomycin; D000001:Calcimycin; D002118:Calcium