RET/PTC1 oncogene signaling in PC Cl 3 thyroid cells requires the small GTP-binding protein Rho

Oncogene. 2001 Oct 25;20(48):6973-82. doi: 10.1038/sj.onc.1204886.


Thyroid papillary carcinomas are characterized by RET/PTC rearrangements that cause the tyrosine kinase domain of the RET receptor to fuse with N-terminal sequences encoded by heterologous genes. This results in the aberrant expression of a ligand-independent and constitutively active RET kinase. We analysed actin reorganization induced by the RET/PTC1 oncogene in PC Cl 3 rat thyroid epithelial cells. Differently from oncogenes Src, Ras and Raf, RET/PTC1 caused actin filaments to form prominent stress fibers. Moreover, stress fibers were identified in human thyroid papillary carcinoma cell lines harboring RET/PTC1 rearrangements but not in thyroid carcinoma cells negative for RET/PTC rearrangements. RET/MEN 2A, a constitutively active but unrearranged membrane-bound RET oncoprotein, did not induce stress fibers in PC Cl 3 cells. Induction of stress fibers by RET/PTC1 was restricted to thyroid cells; it did not occur in NIH3T3 fibroblasts or MCF7 mammary cells. RET/PTC1-mediated stress fiber formation depended on Rho but not Rac small GTPase activity. In addition, inhibition of Rho, but not of Rac, caused apoptosis of RET/PTC1-expressing thyroid cells. We conclude that Rho is implicated in the actin reorganization and cell survival mediated by the chimeric RET/PTC1 oncogene in thyroid epithelial cells, both phenotypes being cell type- and oncogene type-specific.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Apoptosis
  • Breast Neoplasms / pathology
  • Carcinoma, Papillary / pathology*
  • Cell Line
  • Cell Line, Transformed
  • Cell Survival
  • DNA Replication
  • Dimerization
  • Drosophila Proteins*
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2a / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins, Fusion / physiology*
  • Organ Specificity
  • Phenotype
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Rats
  • Receptor Protein-Tyrosine Kinases
  • Recombinant Fusion Proteins / physiology
  • Signal Transduction / physiology*
  • Stress Fibers / physiology*
  • Thyroid Gland / cytology*
  • Thyroid Neoplasms / pathology*
  • Transfection
  • Tumor Cells, Cultured
  • rho GTP-Binding Proteins / physiology*


  • Actins
  • Drosophila Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Ret protein, mouse
  • Ret protein, rat
  • ret-PTC fusion oncoproteins, human
  • rho GTP-Binding Proteins