Mv. Barone et al., RET/PTC1 oncogene signaling in PCCl 3 thyroid cells requires the small GTP-binding protein Rho, ONCOGENE, 20(48), 2001, pp. 6973-6982
Thyroid papillary carcinomas are characterized by RET/PTC rearrangements th
at cause the tyrosine kinase domain of the RET receptor to fuse with N-term
inal 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 lin
es harboring RET/PTC1 rearrangements but not in thyroid carcinoma cells neg
ative for RET/PTC rearrangements. RET/MEN 2A, a constitutively active but u
nrearranged membrane-bound RET oncoprotein, did not induce stress fibers in
PC CI 3 cells. Induction of stress fibers by RET/PTC1 was restricted to th
yroid 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 apo
ptosis of RET/PTC1-expressing thyroid cells. We conclude that Rho is implic
ated 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.