Expression of TRK-T1 oncogene induces differentiation of PC12 cells.
The TRK-T1 oncogene, isolated from a human thyroid carcinoma, represents a rearranged form of the high affinity nerve growth factor (NGF) receptor encoded by the NTRK1 gene; it is created by an intrachromosomal rearrangement fusing the NTRK1 tyrosine kinase domain to the 5' portion of the TPR gene. We have investigated the effect of the TRK-T1 oncogene in PC12 cells, a model system for studying neuronal differentiation and the mechanism of action of NGF. Here, we report that, in PC12 cells, the TRK-T1 oncogene has a differentiating effect that resembles that of NGF and requires the phosphorylation of the oncoprotein. Our results are consistent with the hypothesis that TRK-T1, as well as the original TRK oncogene, induces PC12 differentiation by mimicking the action of NGF bound to its receptor.
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
A
A
Greco
R
R
Orlandi
C
C
Mariani
C
C
Miranda
M G
MG
Borrello
A
A
Cattaneo
S
S
Pagliardini
M A
MA
Pierotti
D000818:Animals; D001483:Base Sequence; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D005822:Genetic Vectors; D026121:Indole Alkaloids; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology*; D009857:Oncogenes / Q000502:physiology*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors; D014162:Transfection / Q000502:physiology
D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; C049985:staurosporine aglycone; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA