Stable expression of intracellular Notch suppresses v-Src-induced transformation in avian neural cells
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ABSTRACT: We reported that stable expression of constitutively active intra cellular Notch (ICN), in quail neuroretina (QNR) cells transformed by a conditional v-Src mutant (QNR/v-src cells), resulted in the suppression of their transformed properties. Acquisition of a normal phenotype coincided with a major switch in cell identity, as these undifferentiated QNR/v-src cells acquired characteristics of glial differentiation. Similar loss of transformation and gene reprogramming can be achieved in QNR/v-src cells, stably expressing the human CBF protein, RBP-Jk, whose activity was rendered ligand independent by fusion to the VP16 transactivator. These major phenotypic changed are correlated with a dominant interference with signaling effectors, regulating cell morphology and cytoskeleton organization. To understand the mechanisms by which Notch signaling activation suppressed v-Src induced cell transformation and induced differentiation, we compared the transcription profile of QNR cells transformed by a v-Src mutant encoding a temperature sensitive oncoprotein (QNR/v-src), with that of cells stably expressing ICN (QNR/v-src/ICN) or RBP-Jk-VP16 (QNR/v-src/RBP-Jk-VP16). Total RNA was extracted from QNR/v-src, QNR/v-src/ICN or QNR/v-src/RBP-Jk-VP16 cells maintained at permissive (37°C) or restrictive (41°C) temperature. cDNA from QNR/v-src cells was probed with that of QNR/v-src/ICN or QNR/v-src/RBP-Jk-VP16 at both temperature on microarrays spotted with 13,000 cDNA from chicken EST collections designed by the genomic facility of the Fred Hutchinson Cancer Research Center (Seattle). For two sets of sample, dye swap experiments were performed.
ORGANISM(S): Gallus gallus
SUBMITTER: georges calothy
PROVIDER: E-GEOD-22054 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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