Journal of Neuro-Oncology 6:269-2"/6 (1988) © Kluwer Academic Publishers - Printed in the Netherlands 269 The effects of type beta transforming growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma cell line Eirik Helseth, Geirmund Unsgaard 1, Are Dalen 2 and Randi Vik qnstitute of Cancer Research, Department of Neurosurgery; 2Department of Virology, University of Trondheim, Tronheim Regional Hospital, N-7000 Trondheim, Norway Key words: glioma, growth factors, receptors,, autocrine growth Summary Type beta transforming growth factor (B-TGF) is a potent growth inhibitor to many human tumor cell lines. Very little is known about the mechanism for this growth inhibitory action of B-TGE We here report the effect of B-TGF on proliferation and epidermal growth factor receptor (R-EGF) expression in a human glioblastoma cell line named T-MG1. B-TGF inhibite the soft agar growth of T-MG1 cells. Maximum inhibition was 70%, achieved with 0.5 units B-TGE B-TGF had no effect on monolayer growth of T-MG1 cells. T-MG1 cells contained abundant R-EGF, which could be divided into two subpopulations, one high affinity and one low affinity population of R-EGF. Treatment with B-TGF caused an initial decrease (0- 6 h) in EGF- binding, followed by an increase in EGF-binding which reached maximum after 24 h exposure to B-TGF. Since addition of EGF to agar cultures gave no additional increase in inhibition by B-TGF and EGF alone had no inhibitory effect, we believe that binding of EGF to its receptor is not part of the pathway mediating the inhibito- ry effect of B-TGF. All neoplastic cells have lost some measure of growth control and the cellular elements involved are growth factors, growth factor receptors and oncogenes. T-MG1 cells contain abundant R-EGF and this may partly explain their malignant nature (malignant nature is here defined as ability to proliferate in agarose). Type alpha transforming growth factors, which in some cancer cells act as uncontrolled autocrine growth factors, were not found in protein extracts from T-MG1 cells. B-TGF, which is normally found in all cells, could not be detect- ed in protein extracts from T-MG1 cells. The lack of B-TGF as an autocrine growth inhibitor may be of impor- tance for maintaining the malignant nature of T-MG1 cells. Introduction Type beta transforming growth factor (B-TGF), a hormonally active polypeptide found in normal and transformed tissues [1, 2], is a potent regulator of cell growth [1- 5] and differentiation [1, 6, 7]. The name 'transforming growth factor (TGF)' was given to B-TGF because of its ability to induce transformed growth in fibroblastic indicator cells [8]. However, the name 'TGF' is a misnomer, since, depending on the assay system, B-TGF is often neither 'a trans- forming factor' nor a 'growth factor'. With regard to growth the effects of B-TGF are bifunctional, and whether its action is growth stimulatory or growth in- hibitory depends on the cell type, growth conditions and the simultaneous action of other growth factors [51. B-TGF is a potent inhibitor of the anchorage in- dependent growth of many human tumor cell lines [1, 3, 51. Very little is known about the mechanism