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CHANG, Hsiu-Hao; LEE, Hsinyu; HUANG, Shiu-Feng; TSAY, Yeou-Guang; HSIEH, Fon-Jou; LIN, Kai-Hsin; HSU, Wen-Ming; LIAO, Yung-Feng; HU, Ming-Kuan; TSAO, Po-Nien; JUAN, Hsueh-Fen; HUANG, Min-Chuan; SHIH, Yu-Yin; WANG, Bo-Jeng; JENG, Yung-Ming; CHRISTINA LING CHANG
Clinical cancer research, 09/2010, Letnik: 16, Številka: 17Journal Article
Notch signaling has been implicated to play a critical role in the tumorigenesis of neuroblastoma (NB) and can modulate calreticulin (CRT) expression that strongly correlates with tumor differentiation and favorable prognosis of NB. We thus sought to determine how Notch regulates CRT expression and affects NB tumor behavior. The Notch-dependent regulation of CRT expression in cultured NB cells was analyzed by confocal microscopy and Western blotting. Notch1 protein expression in 85 NB tumors was examined by immunohistochemistry and correlated with the clinicopathologic/biological characters of NB patients. The progression of NB tumors in response to attenuated Notch signaling was examined by using a xenograft mouse model. We showed that CRT is essential for the neuronal differentiation of NB cells elicited by inhibition of Notch signaling. This effect was mediated by a c-Jun-NH(2)-kinase-dependent pathway. Furthermore, NB tumors with elevated Notch1 protein expression were strongly correlated with advanced tumor stages, MYCN amplification, an undifferentiated histology, as well as a low CRT expression level. Most importantly, the opposing effect between Notch1 and CRT could reciprocally affect the survival of NB patients. The administration of a gamma-secretase inhibitor into a xenograft mouse model of NB significantly suppressed the tumor progression. Our findings provide the first evidence that a c-Jun-NH(2)-kinase-CRT-dependent pathway is essential for the neuronal differentiation elicited by Notch signaling blockade and that Notch1 and CRT can synergistically predict the clinical outcomes of NB patients. The present data suggest that Notch signaling could be a therapeutic target for NB.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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