PMID- 8780892
OWN - NLM
STAT- MEDLINE
DCOM- 19970117
LR  - 20131121
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 7
IP  - 6
DP  - 1996 Jun
TI  - Regulation by retinoic acid of insulin-degrading enzyme and of a related 
      endoprotease in human neuroblastoma cell lines.
PG  - 787-96
AB  - Physiologically, the action of insulin-like growth factors (IGFs) is controlled 
      at different levels, from its transcription start by tissue-specific and 
      development-specific transcriptional factors to its degradation by peptidases 
      such as insulin-degrading enzyme (IDE). Since IGF-II is the major 
      autocrine/paracrine growth factor for neuroblastoma cells, we studied the 
      expression and the role of IDE in this system. Here, we show that (a) IDE is 
      expressed in several human neuroectodermal tumor cell lines, including 
      neuroblastoma cell lines; (b) in a neuroblastoma cell line, IDE expression is 
      up-regulated by retinoic acid, a well-known inducer of neuronal differentiation 
      and/or programmed cell death; (c) IDE is probably not the only IGF-degrading 
      enzyme present in these cells, since the activity of a novel thermolysin-like 
      metalloendopeptidase, clearly distinct from IDE, is also detected. The TME 
      activity is inhibited by IGF-I, Des-IGF-I, and IGF-II, and it is down-regulated 
      by retinoic acid. Since retinoic acid plays a relevant role in controlling the 
      growth of these cells and affects the expression of IDE, we have also: (a) 
      identified the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) 
      expressed in these cell lines and (b) by means of synthetic retinoid analogues 
      identified the RAR/RXR isoforms whose activation may be sufficient to induce the 
      expression of the IDE gene. These results provide evidence that complex 
      posttranslational molecular mechanisms participate in the autocrine/paracrine 
      growth control of the IGF-II loop in neuroblastomas involving proteolytic 
      systems.
FAU - Melino, G
AU  - Melino G
AD  - Biochemistry Laboratory, IDI-IRCCS, C10 Department of Experimental Medicine, 
      University of Rome, Tor Vergata, Italy.
FAU - Draoui, M
AU  - Draoui M
FAU - Bernardini, S
AU  - Bernardini S
FAU - Bellincampi, L
AU  - Bellincampi L
FAU - Reichert, U
AU  - Reichert U
FAU - Cohen, P
AU  - Cohen P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.24.27 (Thermolysin)
RN  - EC 3.4.24.56 (Insulysin)
SB  - IM
MH  - Endopeptidases/*drug effects
MH  - Humans
MH  - Insulysin/*drug effects
MH  - Molecular Structure
MH  - Neuroblastoma
MH  - Neuroectodermal Tumor, Melanotic/enzymology/metabolism
MH  - Thermolysin/metabolism
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1996 Jun;7(6):787-96.