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Molecular characterization of Patched ‐associated rhabdomyosarcoma
Author(s) -
Kappler Roland,
CalzadaWack Julia,
Schnitzbauer Udo,
Koleva Milena,
Herwig Astrid,
Piontek Guido,
Graedler Florian,
Adamski Jerzy,
Heinzmann Ulrich,
Schlegel Jürgen,
Hemmerlein Bernhard,
QuintanillaMartinez Leticia,
Hahn Heidi
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1361
Subject(s) - ptch1 , medulloblastoma , biology , rhabdomyosarcoma , gli1 , cancer research , mutant , cell growth , carcinogenesis , microbiology and biotechnology , hedgehog , gene , genetics , signal transduction , pathology , sarcoma , medicine
Mutations in the human homologue of Drosophila Patched1 ( PTCH1 ) have been found in several common tumours including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma (RMS). Medulloblastoma and RMS are also present in the murine model for Ptch1 deficiency. Tumours in heterozygous Ptch1 neo 67/+ mice consistently exhibit elevated transcript levels of the proto‐oncogene Gli1 , of Ptch1 itself, and of the insulin‐like growth factor 2 ( Igf2 ). The present study has investigated additional molecular changes in RMSs of Ptch1 mutant mice by means of microarray analysis and protein expression analysis. The data show activation of the cell survival‐promoting Akt/protein kinase B (Pkb). Furthermore, RMSs express increased levels of the anti‐apoptotic protein Bcl‐2 and of genes and proteins known to inhibit cell proliferation, including Gadd45a and p27 kip1 . Taken together, the data suggest that the formation of RMSs in Ptch1 mutants is associated with the ability of tumour cells to resist apoptosis. Copyright © 2003 John Wiley & Sons, Ltd.