An aberrant autocrine activation of the platelet-derived growth factor alpha-receptor in follicular and papillary thyroid carcinoma cell lines.
Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.
Chen
Kuei-Tien
KT
School of Medical Technology, Chang Gung University, Taoyuan, Taiwan.
Lin
Jen-Der
JD
Liou
Miaw-Jene
MJ
Weng
Hsiao-Fen
HF
Chang
C Allen
CA
Chan
Err-Cheng
EC
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism*; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism*; D019898:Autocrine Communication; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D018076:DNA, Complementary; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D020032:Tyrphostins; C075278:platelet-derived growth factor A; D014443:Tyrosine; D020796:Receptor, Platelet-Derived Growth Factor alpha