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J. Biol. Chem., Vol. 277, Issue 39, 36715-36724, September 27, 2002
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From the The phenotype of neurosecretory cells is
characterized by clear vesicles and dense granules, both discharged by
regulated exocytosis. However, these organelles are lacking
completely in a few neurosecretion-incompetent clones of the
pheochromocytoma PC12 line, in which other specific features are
maintained (incompetent clones). In view of the heterogeneity of PC12
cells, a differential characterization of the incompetent phenotype
based on the comparison of a single incompetent and a single wild-type
clone would have been inconclusive. Therefore, we have compared two
pairs of PC12 clones, studying in parallel the transcript levels of
4,200 genes and 19,000 express sequence tags (ESTs) by high density
oligonucleotide arrays. After accurate data processing for quality
control and filtration, a total of 755 transcripts, corresponding to
448 genes and 307 ESTs, was found consistently changed, with 46%
up-regulated and 54% down-regulated in incompetent versus
wild-type clones. Many but not all neurosecretion genes were profoundly
down-regulated in incompetent cells. Expression of endocytosis genes
was normal, whereas that of many nuclear and transcription factors,
including some previously shown to play key roles in neurogenesis, was
profoundly changed. Additional differences appeared in genes involved
in signaling and metabolism. Taken together these results
demonstrate for the first time that expression of neurosecretory
vesicles and granules is part of a complex gene expression program that includes many other features that so far have not been recognized.
Neurosecretion Competence
A COMPREHENSIVE GENE EXPRESSION PROGRAM IDENTIFIED IN PC12
CELLS*,
§,
,, and Central Nervous System, F. Hoffmann-La Roche
Ltd., Grenzacherstrasse, Basel 4070, Switzerland and the
¶ Vita-Salute San Raffaele University and Department of
Neuroscience, § San Raffaele Scientific
Institute, Department of Biological and Technological Research, Via
Olgettina, 58, Milano 20132, Italy
*
This work, supported by grants from the European Union
(Growbeta), the Italian Ministry of University and Research (COFIN and
FIRB programs), Telethon (project 1118), and the Armenise-Harvard Foundation, was carried out in the Center of Excellence in
Physiopathology in Cell Differentiation, awarded to the Vita-Salute San
Raffaele University by the Italian Ministry of University and Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The on-line version of this article (available at
http://www.jbc.org) contains Fig. S1 and Tables I-III.
§
Both authors contributed equally to this work.
To whom correspondence may be addressed. Tel.:
39-02-2643-2913; Fax: 39-02-2643-2914; E-mail:
malosio.marialuisa@hsr.it.
**
To whom correspondence may be addressed. Tel.: 39-02-2643-2770;
Fax: 39-02-2643-4813; E-mail: meldolesi.jacopo@hsr.it.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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