In:
Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 6, No. 3 ( 2008-03-01), p. 468-482
Kurzfassung:
Sprouty (Spry) proteins modulate signal transduction pathways elicited by receptor tyrosine kinases (RTK). Depending on cell type and the particular RTK, Spry proteins exert dual functions: They can either repress RTK-mediated signaling pathways, mainly by interfering with the Ras/Raf/mitogen-activated protein kinase pathway or sustaining RTK signal transduction, for example by sequestering the E3 ubiquitin-ligase c-Cbl and thus preventing ubiquitylation, internalization, and degradation of RTKs. Here, by the inducible expression of murine Spry4 in pancreatic β cells, we have assessed the functional role of Spry proteins in the development of pancreatic islets of Langerhans in normal mice and in the Rip1Tag2 transgenic mouse model of β-cell carcinogenesis. β cell–specific expression of mSpry4 provokes a significant reduction in islet size, an increased number of α cells per islet area, and impaired islet cell type segregation. Functional analysis of islet cell differentiation in cultured PANC-1 cells shows that mSpry4 represses adhesion and migration of differentiating pancreatic endocrine cells, most likely by affecting the subcellular localization of the protein tyrosine phosphatase PTP1B. In contrast, transgenic expression of mSpry4 during β-cell carcinogenesis does not significantly affect tumor outgrowth and progression to tumor malignancy. Rather, tumor cells seem to escape mSpry4 transgene expression. (Mol Cancer Res 2008;6(3):468–82)
Materialart:
Online-Ressource
ISSN:
1541-7786
,
1557-3125
DOI:
10.1158/1541-7786.MCR-07-0255
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2008
ZDB Id:
2097884-4
SSG:
12
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