Excessive activation of tyrosine kinases leads to inhibition of proliferation in a thyroid carcinoma cell line.
Autocrine stimulation of growth is a hallmark of many tumor cell lines. In this work we investigated the synthesis and secretion of growth factors and the expression of their corresponding receptors in HTC-TSHr thyroid carcinoma cells. These cells synthesize epidermal growth factor (EGF) receptors and platelet-derived growth factor beta (PDGF beta) receptors and in addition transforming growth factor alpha (TGF alpha), PDGF-A and PDGF-B chains, respectively. Addition of EGF or PDGF-BB to the culture medium resulted in growth inhibition of HTC-TSHr cells. In contrast, treatment of the cells with low concentrations of neutralizing anti-TGF alpha antibodies or tyrosine kinase inhibitors led to stimulation of cell proliferation. Low concentrations of neutralizing anti-PDGF-B antibodies did not affect growth of the cells. As expected, cell proliferation was inhibited when high concentrations of either neutralizing anti-TGF alpha antibodies or anti-PDGF-B antibodies were applied. PDGF-AA did not influence growth of HTC-TSHr cells. We conclude that growth of HTC-TSHr thyroid carcinoma cells is influenced by two autocrine loops between TGF alpha and EGF receptors and between PDGF-B and PDGF beta receptors. However, our data suggest that excessive activation of tyrosine kinase receptors in these cells results in a relative inhibition rather than stimulation of growth.
Broecker
M
M
Laboratories of Molecular Endocrinology, University Clinic of Internal Medicine, Bergmannsheil, Ruhr University, Bochum, Germany.
Hammer
J
J
Derwahl
M
M
D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D008970:Molecular Weight; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000032:analysis; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor