TRANSFORMING GROWTH FACTOR β2 UP-REGULATES GM-CSF GENE IN HUMAN BLADDER CARCINOMA CELL LINE HTB 5637

Transforming growth factor betas are multifunctional polypeptides in the cytokine superfamily. They have a growth inhibitory role on hemopoietic progenitor cells in semisolid colony assay as well as in long-term bone-marrow culture. TGF - β2 represses stromal cells, stem cell factor gene transcription, and decreases the stability of c-kit transcripts in hemopoietic cells. TGF-β also modulates GM-CSF production from human lymphocytes. The present study reveals the TGF- β2 role in production of GM-CSF in HTB 5637, human bladder carcinoma cell line. HTB 5637 cells were treated with 5 ng/mL of human TGF - β2' viable cells were counted and GM-CSF concentration was determined, No antiproliferate activity of TGF- β2on HTB 5637 cell line was observed. Biological assay showed increased levels of GM-CSF in the supernatant of cultured cells. However this increase was lower than that expected from ELISA. Since TGF- β may be an active suppressor factor regulating hemopoiesis, it seems that some inhibitory factor(s) may be produced (increased) in response to TGF- β2 treatment. It has been shown that GM-CSF mRNA content from HTB 5637 cell line is very stable and this stabilization is translational dependent. Using Slot blot and Northern blot analysis, we determined that TGF- β2 upregulated GM-CSF gene expression in HTB 5637 cell line. The results suggest that TGF- β2 upregulates the production of GM-CSF gene at the transcriptional level.