Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition
dc.contributor.author | Hughes, Dennis P. M. | en_US |
dc.contributor.author | Thomas, Dafydd G. | en_US |
dc.contributor.author | Giordano, Thomas J. | en_US |
dc.contributor.author | McDonagh, Kevin T. | en_US |
dc.contributor.author | Baker, Laurence H. | en_US |
dc.date.accessioned | 2007-05-02T14:19:08Z | |
dc.date.available | 2007-05-02T14:19:08Z | |
dc.date.issued | 2006-05-01 | en_US |
dc.identifier.citation | Hughes, Dennis P.M.; Thomas, Dafydd G.; Giordano, Thomas J.; McDonagh, Kevin T.; Baker, Laurence H. (2006). "Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition." Pediatric Blood & Cancer 46(5): 614-623. <http://hdl.handle.net/2027.42/50677> | en_US |
dc.identifier.issn | 1545-5009 | en_US |
dc.identifier.issn | 1545-5017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/50677 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16007579&dopt=citation | en_US |
dc.description.abstract | Background The role of erbB tyrosine kinases, especially Her-2, in osteosarcoma has engendered intense debate. Some investigators identified an association between low-level Her-2 expression, compared to none, and poor patient outcome. Others questioned the importance of apparent cytoplasmic expression of Her-2, since membranous overexpression is associated with poor outcome in carcinomas. We previously demonstrated that primary osteosarcoma cells express cell-surface EGFR and Her-2, with the p80 isoform of Her-4 localized to the nucleus. We wished to determine if erbB kinases in osteosarcoma were phosphorylated, and if this was required for growth. Procedures We cultured early passage osteosarcoma cell lines in the presence or absence of the pan-erbB inhibitor CI-1033 and examined the phosphorylation status of EGFR, Her-2, and Her-4 by immunohistochemistry, cell-based ELISA, flow cytometry and two dimensional Western blot. We also assessed the impact of CI-1033 upon osteosarcoma growth and survival in vitro. Results EGFR, Her-2, and Her-4 were constitutively phosphorylated in early passage osteosarcoma cells cultured in vitro. CI-1033 abrogated erbB receptor phosphorylation and caused growth inhibition and apoptosis in a titratible fashion with concentrations of 1 ΜM or more. Conclusions EGFR, Her-2, and Her-4 are constitutively phosphorylated in early passage osteosarcoma cells in tissue culture, and erbB signaling provides essential growth and anti-apoptotic signals to osteosarcoma cells. This suggests that erbB overexpression is not required for erbB to promote malignancy, but rather that overexpression is one of several mechanisms that generate unregulated erbB signaling. © 2005 Wiley-Liss, Inc. | en_US |
dc.format.extent | 271609 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pediatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas ; Division of Pediatrics, MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 853, Houston, TX 77030-4009. | en_US |
dc.contributor.affiliationother | Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky | en_US |
dc.identifier.pmid | 16007579 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/50677/1/20454_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/pbc.20454 | en_US |
dc.identifier.source | Pediatric Blood & Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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