Overexpression of c-fos in a human pre-B cell acute lymphocytic leukemia derived cell line, SMS-SB.
The c-fos proto-oncogene is found to be overexpressed at least 30-fold in SMS-SB, a pre-B leukemic cell line compared to other cell types. No gross alteration of the c-fos gene structure in SMS-SB cells can be detected by karyotypic or Southern analyses. C-fos in SMS-SB cells can still be induced by serum, TPA and the calcium ionophore, A23187, and superinduced by the combination of serum and cycloheximide. The elevated levels of c-fos transcripts are not due merely to an increased life span of mRNA, as the half-life of steady state c-fos mRNA in SMS-SB cells is about 40 min. Nuclear run-on transcription assays demonstrate that the transcription rate of c-fos in SMS-SB cells is up-regulated about 30-fold as compared to another pre-B leukemic cell line, NALM-6. In order to determine whether this is a cis- or transacting effect, we sequenced the 550 base pairs upstream of the SMS-SB c-fos coding region and found no mutations upstream of the mRNA CAP site. However, two point mutations at positions +23 and +98, respectively, were found in the 5' noncoding region of the first exon. Consistent with the overexpression of c-fos mRNA, the 55 kD c-fos protein is present in SMS-SB cells through detection by immunoprecipitation, but could not be detected in NALM-6 cells. SMS-SB cells however, do not appear to contain more abundant AP-1 DNA binding activity than NALM-6 cells.
Tsai
L H
LH
CRC Laboratories, Beatson Institute for Cancer Research, Glasgow, UK.
Nanu
L
L
Smith
R G
RG
Ozanne
B
B
D001483:Base Sequence; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D012313:RNA / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; C016276:8-bromocyclic GMP; D000001:Calcimycin; D012313:RNA; D004247:DNA; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate