An aberrant autocrine activation of the platelet-derived growth factor alpha-receptor in follicular and papillary thyroid carcinoma cell lines

Cancer Lett. 2006 Jan 18;231(2):192-205. doi: 10.1016/j.canlet.2005.01.039. Epub 2005 Aug 29.

Abstract

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.

MeSH terms

  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / metabolism*
  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / metabolism*
  • Autocrine Communication*
  • Blotting, Western
  • Cell Proliferation / drug effects
  • DNA, Complementary
  • Enzyme Activation
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • Tyrphostins / pharmacology

Substances

  • DNA, Complementary
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Tyrphostins
  • platelet-derived growth factor A
  • Tyrosine
  • Receptor, Platelet-Derived Growth Factor alpha