Identification of transforming growth factor-beta 1-binding protein overexpression in carmustine-resistant glioma cells by mRNA differential display

BACKGROUND. The authors previously demonstrated the presence of cells in pr imary human malignant gliomas that intrinsically are resistant to carmustin e (BCNU). Numerous studies have identified mechanisms of therapy resistance in these cells; however, the authors' work and that of others suggest that additional mechanisms of resistance exist. METHODS. The authors identified a glioma cell line that lacks detectable me thylguanine methyltransferase expression and does not alter its expression of glutathione-S-transferase-pi in response to BCNU chemotherapy. This cell line was used in mRNA differential display experiments to identify genes i nvolved in what to the authors' knowledge were previously undescribed mecha nisms of resistance. RESULTS. The overexpression of the gene encoding the transforming growth fa ctor latency binding protein was demonstrated in glioma cells selected for resistance to BCNU, compared with their parental unselected cells. CONCLUSIONS. Transforming growth factor-beta 1 has pleiotropic functions in transformed and normal cells. Although activation of TGF-beta 1 does not a ppear to be a causative factor in BCNU resistance in the current study, it may be involved in the growth of these resistant cells. (C) 2000 American C ancer Society.