Platelet-derived growth factor is an autocrine stimulator for the growth and survival of human esophageal carcinoma cell lines.
Platelet-derived growth factors (PDGF) are important mitogens for mesenchyme-derived cells. Neither PDGF nor PDGF receptors (PDGFR) are expressed in epithelial cells under normal physiological conditions. However, we have found that PDGF-BB induces c-jun expression and promotes the growth of the human esophageal carcinoma cell line CE48T/VGH. Scatchard analysis revealed the presence of 6 x 10(5) binding sites for PDGF-BB per cell, with a Kd of 9.7 nM. Furthermore, our data indicate that CE48T/VGH expresses beta type PDGFR (PDGFRbeta) with in vitro auto-kinase activity. We have also found that CE48T/VGH expresses the mRNA of the PDGF-A and PDGF-B chains and secretes PDGF molecules. Addition of anti-PDGF neutralizing antibody significantly decreased cell numbers of CE48T/VGH under serum-free conditions. The detached cells underwent apoptosis characterized by micronucleation. These results suggest that expression of the PDGF autocrine system may not only provide the growth advantage but also prevent the apoptosis for CE48T/VGH.
Institute of Microbiology and Immunology, National Yang-Ming University, Taiwan, Republic of China.
Y C
YC
Liu
S C
SC
Chen
C
C
Chang
C M
CM
Leu
C P
CP
Hu
D017209:Apoptosis; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004938:Esophageal Neoplasms; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor