-transparent.png){kind=logo}
Negative feedback regulation of c-myc gene expression has been observed in some, but not all, cell types. In order to demonstrate conclusively the existence of this mechanism and gain insight into the cause of its inactivation, we have directly examined its function in B cells and then investigated its activity in a number of cell types. We demonstrate the existence of negative c-myc autoregulation by showing the rapid, dose dependent and reversible suppression of endogenous c-myc expression in EBV-immortalized B lymphoblastoid cells transfected with a c-myc gene expressed under the control of a heavy metal inducible promoter. Autoregulation occurs at the level of transcriptional initiation and is mediated by at least one stable intermediate or cofactor molecule. The c-myc autoregulatory mechanism was found operative in all (11 of 11) non-tumorigenic cells tested, including normal and immortalized lymphocytes and fibroblasts. However, this mechanism was found to be inactive in all (10 of 10) tumor cell lines derived from a variety of tissues including those carrying normal and oncogenically activated c-myc genes. These data establish the existence of an important regulatory circuit modulating c-myc expression in normal cells and suggest that its inactivation may represent a general regulatory disturbance of transformed cells.
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
April 1990,
The EMBO journal,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
October 1986,
Canadian journal of genetics and cytology. Journal canadien de genetique et de cytologie,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
December 1989,
Biochemical and biophysical research communications,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
January 1988,
Current topics in microbiology and immunology,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
January 1997,
Molecular and cellular biology,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
April 1985,
Biochemical and biophysical research communications,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
November 1998,
Journal of biochemistry,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
January 1986,
Current topics in microbiology and immunology,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
April 2001,
Cancer research,
F Grignani, and
L Lombardi, and
G Inghirami, and
L Sternas, and
K Cechova, and
R Dalla-Favera
January 2006,
Cancer research,
