Constitutively expressed c-myb abrogates the requirement for insulinlike growth factor 1 in 3T3 fibroblasts.

Abstract

The proto-oncogene c-myb, whose expression is usually limited to cells of the hematopoietic lineages, can be expressed in fibroblasts if placed under the control of a constitutive promoter, such as the simian virus SV40 early promoter. 3T3 cells carrying a constitutively expressed human c-myb were found to grow in 1% serum or in a serum-free, platelet-derived growth factor-supplemented medium, whereas the parent cell line, BALB/c 3T3, needed insulinlike growth factor 1 (IGF-1) in addition to platelet-derived growth factor for growth. myb-carrying cells, however, could not grow in platelet-poor plasma. In fibroblasts, therefore, a constitutively expressed c-myb can abrogate the requirement for platelet-poor plasma or IGF-1. When 3T3 cells constitutively expressed both c-myc and c-myb, they could grow in serum-free medium without added growth factors. The ability of c-myb to abrogate in fibroblasts the IGF-1 requirement seems to be due to its ability to induce overexpression of IGF-1, as indicated by an increase in steady-state levels of IGF-1 mRNA. These results have some important implications; for instance, they suggest a commonality of pathways for entry into S phase in different cell types and the possibility of a myb-like or myb-equivalent gene product of critical importance for entry of fibroblasts into S phase.

Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.

“…The role played by c-myb in smooth muscle proliferation/migration is not understood completely, but the protooncogene appears to be involved in regulating the GI /S phase transition, possibly by initiating an elevation of calcium ion at this stage ofthe cell cycle ( 19,20). In fibroblast cell lines, constitutive overexpression of c-myb posttranscriptionally elevates the levels of PCNA, suggesting that this cell cycle-dependent protein may be a critical link between c-myb and proliferation/migration of various cell types (21 ).…”

HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia

“…[38][39][40] IGF-1R has been reported to be regulated by the c-Myb transcription factor. [25][26][27] In a recent report, expression of MLL/ENL resulted in increased c-Myb expression. 24 In our study, c-Myb levels were increased upon induction of HoxA9 activity.…”

“…[25][26][27] IGF-1R has been reported to relieve leukemic cells of cytokine dependency. 28 However, BLIN-3 cells lack expression of endogenous HoxA9 14 and have retained an absolute requirement for growth factor/ stromal cell contact for optimal growth and proliferation.…”

Myb targeted therapeutics for the treatment of human malignancies

“…Other myb functions of potential signi®cance with regard to hematopoietic cell transformation might relate to Myb's ability to regulate hematopoietic cell proliferation , perhaps by its e ects on important cell cycle genes including c-myc (Cogswell et al, 1993), PCNA (Travali et al, 1991a), and cdc2 (Ku et al, 1993). Finally, Myb also plays a role in regulating hematopoietic cell di erentiation (Caracciolo et al, 1990;Clarke et al, 1988).…”

“…Finally, Myb also plays a role in regulating hematopoietic cell di erentiation (Caracciolo et al, 1990;Clarke et al, 1988). It functions as a transcription factor for several cellular genes including the neutrophil granule protein mim-1 (Ness et al, 1989), CD4 (Nakayama et al, 1993), IGF-1 (Travali et al, 1991b), andCD34 (Melotti andCalabretta, 1994) and possibly other growth factors, including c-kit . The latter is of particular interest since it has been shown that when hematopoietic cells are deprived of c-kit ligand (Steel Factor) they undergo apoptosis (Yu et al, 1993).…”