Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma
Copyright 2010 AACR..
Mouse studies indicate that the synthetic glucocorticoid dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here, we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing the survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of glycogen synthase kinase 3beta, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2010 |
|---|---|
| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
|---|---|
| Enthalten in: |
Cancer research - 70(2010), 13 vom: 01. Juli, Seite 5220-5 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Heine, Vivi M [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.08.2010 Date Revised 25.04.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1158/0008-5472.CAN-10-0554 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM198652461 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM198652461 | ||
| 003 | DE-627 | ||
| 005 | 20231223213130.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2010 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1158/0008-5472.CAN-10-0554 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0662.xml |
| 035 | |a (DE-627)NLM198652461 | ||
| 035 | |a (NLM)20530674 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Heine, Vivi M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma |
| 264 | 1 | |c 2010 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.08.2010 | ||
| 500 | |a Date Revised 25.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright 2010 AACR. | ||
| 520 | |a Mouse studies indicate that the synthetic glucocorticoid dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here, we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing the survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of glycogen synthase kinase 3beta, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Hedgehog Proteins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-myc |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a Glycogen Synthase Kinase 3 beta |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Gsk3b protein, mouse |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Glycogen Synthase Kinase 3 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.26 |2 NLM | |
| 700 | 1 | |a Priller, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Rowitch, David H |e verfasserin |4 aut | |
| 700 | 1 | |a Schüller, Ulrich |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer research |d 1945 |g 70(2010), 13 vom: 01. Juli, Seite 5220-5 |w (DE-627)NLM000001740 |x 1538-7445 |7 nnns |
| 773 | 1 | 8 | |g volume:70 |g year:2010 |g number:13 |g day:01 |g month:07 |g pages:5220-5 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1158/0008-5472.CAN-10-0554 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 70 |j 2010 |e 13 |b 01 |c 07 |h 5220-5 | ||