Notch signaling activation suppresses v-Src-induced transformation of neural cells by restoring TGF-β-mediated differentiation.
BACKGROUND
We have been investigating how interruption of differentiation contributes to the oncogenic process and the possibility to reverse the transformed phenotype by restoring differentiation. In a previous report, we correlated the capacity of intracellular Notch (ICN) to suppress v-Src-mediated transformation of quail neuroretina (QNR/v-src(ts)) cells with the acquisition by these undifferentiated cells of glial differentiation markers.


RESULTS
In this work, we have identified autocrine TGF-β3 signaling activation as a major effector of Notch-induced phenotypic changes, sufficient to induce transition in differentiation markers expression, suppress morphological transformation and significantly inhibit anchorage-independent growth. We also show that this signaling is constitutive of and contributes to ex-vivo autonomous QNR cell differentiation and that its down-regulation is essential to achieve v-Src-induced transformation.


CONCLUSIONS
These results support the possibility that Notch signaling induces differentiation and suppresses transformation by a novel mechanism, involving secreted proteins. They also underline the importance of extracellular signals in controlling the balance between normal and transformed phenotypes.
CNRS UMR3347/INSERM U1021, Institut Curie-Section Recherche, Orsay, France.
Samira
S
Amarir
Maria
M
Marx
Georges
G
Calothy
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D003370:Coturnix; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D018994:Myosin Light Chains / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors* / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018994:Myosin Light Chains; D012333:RNA, Messenger; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D015688:Oncogene Protein pp60(v-src)