TUMORIGENIC CONVERSION OF HUMAN MESOTHELIAL CELLS AS A CONSEQUENCE OFPLATELET-DERIVED GROWTH FACTOR-A CHAIN OVEREXPRESSION

Overexpression of platelet-derived growth factor (PDGF)-A as well as P DGF-B chain mRNA has previously been reported in human mesothelioma ce ll lines. In this report, it has been established that the A but not t he B chain protein is expressed at detectable levels in cell lysates a nd conditioned medium from these cell lines. In order to investigate t he effect of overexpression of PDGF-A chain in a human mesothelial cel l model system, a retroviral vector containing a human PDGF-A chain cD NA insert under the control of the Moloney murine leukemia virus (MoML V) promoter was inserted into the SV-40 T-antigen immortalized human m esothelial cell line MeT-5A. Selected cells showed overexpression of P DGF-A chain relative to MeT-5A and induced tumors in athymic nude mice . PDGF-A chain overexpression was also found in the tumor specimens ex cised from the mice. PDGF-A mRNA and protein were expressed at a highe r level in the tumor explant cell lines, suggesting a correlation of t umorigenicity with A chain production.