Tumorigenic conversion of human mesothelial cells as a consequence of platelet-derived growth factor-A chain overexpression.
Overexpression of platelet-derived growth factor (PDGF)-A as well as PDGF-B chain mRNA has previously been reported in human mesothelioma cell lines. In this report, it has been established that the A but not the B chain protein is expressed at detectable levels in cell lysates and conditioned medium from these cell lines. In order to investigate the effect of overexpression of PDGF-A chain in a human mesothelial cell model system, a retroviral vector containing a human PDGF-A chain cDNA insert under the control of the Moloney murine leukemia virus (MoMLV) promoter was inserted into the SV-40 T-antigen immortalized human mesothelial cell line MeT-5A. Selected cells showed overexpression of PDGF-A chain relative to MeT-5A and induced tumors in athymic nude mice. PDGF-A chain overexpression was also found in the tumor specimens excised from the mice. PDGF-A mRNA and protein were expressed at a higher level in the tumor explant cell lines, suggesting a correlation of tumorigenicity with A chain production.
Van der Meeren
A
A
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Seddon
M B
MB
Betsholtz
C A
CA
Lechner
J F
JF
Gerwin
B I
BI
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000209:etiology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A