Abstract |
We previously found that a minor subfraction of the human genomic DNA, corresponding to 2500-3000 nonrepetitive sequences of 3 kilobases each and designated as tumor-activated DNA (TaDNA) was transcriptionally active in Burkitt's lymphoma cells and almost inactive in normal lymphocytes growing in vitro following integration of the Epstein-Barr virus genome. Furthermore all the neoplastic cells in culture or primary neoplasms ( leukemias, sarcomas, carcinomas) studied contained transcripts from most of the TaDNA sequences found in malignant lymphoblasts whereas normal cells growing in vitro contained only a few TaDNA transcripts. It is shown in the present study that treatments of the myeloid leukemia HL60 cells with various inducers of cell differentiation ( dimethyl sulfoxide, retinoic acid, mezerein, 12-O-tetradecanoylphorbol-13- acetate, teleocidin) caused a dose-dependent reduction of the level of TaDNA transcripts, correlated with the diminution of c-myc transcripts. The 12-O-tetradecanoylphorbol-13-acetate treatment had this same effect on Burkitt's lymphoma cells (Raji or Namalwa) but the opposite effect on normal cells (Epstein-Barr virus-immortalized lymphocytes or fetal fibroblasts) where it enhanced the formation of Ta- DNA transcripts up to the levels found in untreated malignant cells. These data suggest two conclusions (a) TaDNA corresponds to a multigenic set which seems to be involved in modulation of the malignant phenotype and (b) depending on the origin of the cells, agents like 12-O-tetradecanoylphorbol-13-acetate may operate either as tumor promoters or as differentiation inducers through the control of TaDNA expression.
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Authors | N Hanania, M Castagna, D Shaool, D Zeliszewski, J Harel |
Journal | Cancer research
(Cancer Res)
Vol. 45
Issue 12 Pt 1
Pg. 6058-62
(Dec 1985)
ISSN: 0008-5472 [Print] United States |
PMID | 3933820
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Actins
- Carcinogens
- DNA, Neoplasm
- Diterpenes
- HLA-DR Antigens
- Histocompatibility Antigens Class II
- Lyngbya Toxins
- Terpenes
- teleocidins
- mezerein
- Tretinoin
- Tetradecanoylphorbol Acetate
- Dimethyl Sulfoxide
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Topics |
- Actins
(genetics)
- Burkitt Lymphoma
- Carcinogens
(pharmacology)
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Cell Line
- DNA, Neoplasm
(genetics)
- Dimethyl Sulfoxide
(pharmacology)
- Diterpenes
- Gene Expression Regulation
(drug effects)
- HLA-DR Antigens
- Histocompatibility Antigens Class II
(genetics)
- Humans
- Lyngbya Toxins
(pharmacology)
- Proto-Oncogenes
- Terpenes
(pharmacology)
- Tetradecanoylphorbol Acetate
(pharmacology)
- Transcription, Genetic
(drug effects)
- Tretinoin
(pharmacology)
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