G. Zeng et al., INDUCTION OF PROTOONCOGENES DURING 3-DEAZAADENOSINE-STIMULATED DIFFERENTIATION OF 3T3-L1 FIBROBLASTS TO ADIPOCYTES - MIMICRY OF INSULIN ACTION, Oncology research, 9(4), 1997, pp. 205-211
3-Deazaadenosine (DZA) mimicked the molecular action of insulin in the
induction of 3T3-L1 fibroblasts to differentiate into adipocytes. The
molecular effects of DZA were compared with insulin, which served as
a positive control, on the expression of proto-oncogenes during the in
itial stage of differentiation of 3T3-L1 fibroblasts. Treatment of con
fluent 3T3-L1 fibroblasts with DZA or insulin produced a rapid but tra
nsient expression of mRNA for proto-oncogenes c-fos and c-jun within 3
0-60 min. The mRNA of c-myc increased for 2 h and then decreased 4 h a
fter treatment. Electrophoretic mobility shift assays showed a heighte
ned increase in the appearance of transcription factors AP-1 and AP-2.
The increase was detectable as early as 1 h after the treatment with
either DZA or insulin and was maintained for 6 h. 3T3-L1 cells stably
transfected with the promotor of c-fos linked to a CAT reporter gene s
howed an increase in CAT activity in response to DZA in a time-and dos
e-dependent manner. In cells stably transfected with antisense c-fos,
neither DZA nor insulin was able to induce a differentiation response.
The early transcription of c-fos, c-jun, and c-myc proto-oncogenes an
d the increased expression of transcription factors AP-1 and AP-2, ind
uced by DZA and insulin, appear to be crucial events in the differenti
ation of the 3T3-L1 fibroblasts to adipocytes.