Schaefer, Karl-Ludwig and Brachwitz, Kristin and Braun, Yvonne and Diallo, Raihanatou and Wai, Daniel H. and Zahn, Susanne and Schneider, Dominik T. and Kuhnen, Cornelius and Vollmann, Arabel and Brockhoff, Gero and Gabbert, Helmut E. and Poremba, Christopher (2006) Constitutive activation of neuregulin/ERBB3 signaling pathway in clear cell sarcoma of soft tissue. NEOPLASIA, 8 (7). pp. 613-622. ISSN 1522-8002,
Full text not available from this repository. (Request a copy)Abstract
Clear cell sarcoma of soft tissue (CCSST) represents a highly malignant tumor of the musculoskeletal system that is characterized by the chromosomal translocation t(12;22)(q13;q12) of the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1). In a former microarray expression study, we identified ERBB3, a member of the epidermal growth factor receptor ( EGFR) family, as a promising new diagnostic marker in the differential diagnosis of CCSST. Here we show that, besides ErbB3, all CCSST cell lines (n = 8) also express the ErbB2 receptor or the ErbB4 receptor, representing an adequate coreceptor of ErbB3. The phosphorylation status of ErbB3 revealed these receptor pairs to be either constitutively activated in CCSST cells with high neuregulin-1 (NRG1) expression ( n = 4) or activatable by exogenic NRG1 in cells showing low amounts of NRG1 mRNA ( n = 4). Exogenous NRG1 stimulated the growth of a subset of CCSST cells but did not affect the kinetics of another subset. This difference was not strictly dependent on endogenous NRG1 expression; however, the growth-inhibiting effect of the pan-ErbB tyrosine kinase inhibitor CI-1033 or PD158780 clearly correlated with NRG1 expression indicating an autocrine growth stimulation loop, which may constitute an interesting target of new therapeutic strategies in this tumor entity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPARATIVE GENOMIC HYBRIDIZATION; STANDARD REFERENCE INTERVALS; MALIGNANT-MELANOMA; EXPRESSION ANALYSIS; ERBB RECEPTORS; EWINGS-SARCOMA; CANCER; TUMORS; FAMILY; PARTS; clear cell sarcoma of soft tissue; CGH; ERBB; neuregulin; tyrosine kinase |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Feb 2021 09:55 |
| Last Modified: | 11 Feb 2021 09:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34395 |
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