Recessive genetic deregulation abrogates c-myc suppression by interferon and is implicated in oncogenesis
Previously the authors demonstrated that many hematopoietic tumor cells are resistant to the inhibitory effects that interferon exerts on c-myc mRNA expression without losing other receptor-mediated intracellular responses. They report here that this partial resistance was overridden in two independent stable somatic cell hybrids prepared by fusion between sensitive and resistant cells. The c-myc mRNA transcribed from the active allele of the resistant parent cell was reduced by interferon within the context of the cell hybrid. It was therefore concluded that changes in the cis-acting sequences of c-myc were not involved in this type of relaxed regulation and that resistance resulted rather from inactivation or loss of postreceptor elements which operate in trans. The growth-stimulating effect that this genetic deregulation might have on cells was tested in experimental systems of cell differentiation in which an autocrine interferon is produced. For that purpose the authors isolated variant clones of M1 myeloid cells which were partially resistant to alpha and beta interferons and tested their growth behaviour during in vitro-induced differentiation. The resistant clones displayed higher proliferative activity on days 2 and 3 of differentiation than did the sensitive clones, which stopped proliferating. The loss of c-myc responses to the self-produced interferon disrupted the normal cessation of growth during differentiation and therefore might lead cells along the pathway of neoplasia.
- Research Organization:
- Dept. of Virology, Weizmann Institute of Science, Rehovot (IL)
- OSTI ID:
- 6470913
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 8:7
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW CELLS
CELL DIFFERENTIATION
INTERFERON
BIOLOGICAL FUNCTIONS
ONCOGENIC TRANSFORMATIONS
BIOLOGICAL PATHWAYS
TUMOR CELLS
BIOLOGICAL ADAPTATION
CARCINOGENESIS
CELL PROLIFERATION
CLONE CELLS
EXPERIMENTAL DATA
GENE REGULATION
GENE REPRESSORS
HYBRIDIZATION
HYBRIDOMAS
SOMATIC CELLS
ANIMAL CELLS
CELL CULTURES
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DATA
FUNCTIONS
GROWTH FACTORS
INFORMATION
LYMPHOKINES
MITOGENS
NUCLEOPROTEINS
NUMERICAL DATA
ORGANIC COMPOUNDS
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550200* - Biochemistry