This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bradley, S. V. Articles by Ross, T. S. Search for Related Content PubMed PubMed Citation Articles by Bradley, S. V. Articles by Ross, T. S.

Huntingtin Interacting Protein 1 Is a Novel Brain Tumor Marker that Associates with Epidermal Growth Factor Receptor

¹ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan and ² Department of Surgery (Neurosurgery), Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Theodora S. Ross, University of Michigan, 6322 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0942. Phone: 734-615-5509; E-mail: tsross{at}umich.edu.

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 ß 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. [Cancer Res 2007;67(8):3609–15]

This article has been cited by other articles:

				C. W. Graves, S. T. Philips, S. V. Bradley, K. I. Oravecz-Wilson, L. Li, A. Gauvin, and T. S. Ross Use of a Cryptic Splice Site for the Expression of Huntingtin Interacting Protein 1 in Select Normal and Neoplastic Tissues Cancer Res., February 15, 2008; 68(4): 1064 - 1073. [Abstract] [Full Text] [PDF]

				S. V. Bradley, M. R. Smith, T. S. Hyun, P. C. Lucas, L. Li, D. Antonuk, I. Joshi, F. Jin, and T. S. Ross Aberrant Huntingtin Interacting Protein 1 in Lymphoid Malignancies Cancer Res., September 15, 2007; 67(18): 8923 - 8931. [Abstract] [Full Text] [PDF]