Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor Journal Article


Authors: Bradley, S. V.; Holland, E. C.; Liu, G. Y.; Thomas, D.; Hyun, T. S.; Ross, T. S.
Article Title: Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor
Abstract: Huntingtin interacting protein 1 (HIP1) is a multidomain oncoprotein whose expression correlates with increased epidermal growth factor receptor (EGFR) levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1-positive breast cancers have elevated EGFR protein levels. The combined association of HIP1 with huntingtin, the protein that is mutated in Huntington's disease, and the known overexpression of EGFR in glial brain tumors prompted us to explore HIP1 expression in a group of patients with different types of brain cancer. We report here that HIP1 is overexpressed with high frequency in brain cancers and that this overexpression correlates with EGFR and platelet-derived growth factor β receptor expression. Furthermore, serum samples from patients with brain cancer contained anti-HIP1 antibodies more frequently than age-matched brain cancer-free controls. Finally, we report that HIP1 physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIP1. These findings suggest that HIP1 may up-regulate or maintain EGFR overexpression in primary brain tumors by directly interacting with the receptor. This novel HIP1-EGFR interaction may work with or independent of HIP1 modulation of EGFR degradation via clathrin-mediated membrane trafficking pathways. Further investigation of HIP1 function in brain cancer biology and validation of its use as a prognostic or predictive brain tumor marker are now warranted. ©2007 American Association for Cancer Research.
Keywords: controlled study; human tissue; protein expression; unclassified drug; oncoprotein; dna-binding proteins; cancer patient; brain tumor; glioma; brain neoplasms; protein degradation; epidermal growth factor receptor; tumor markers, biological; protein binding; receptor, epidermal growth factor; tumor marker; brain; immunoprecipitation; actins; lipid metabolism; antibodies, neoplasm; clathrin; huntington chorea; huntingtin interacting protein 1
Journal Title: Cancer Research
Volume: 67
Issue: 8
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2007-04-15
Start Page: 3609
End Page: 3615
Language: English
DOI: 10.1158/0008-5472.can-06-4803
PUBMED: 17440072
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus"
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  1. Eric Holland
    224 Holland