Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer

BMC Cancer

Research Article

Gabriele B Beck-Engeser¹  Matthias Wabl¹  Amy M Lum²  Lauri Li²  Namitha Channa²  Bruce B Wang² 

[1] Department of Microbiology and Immunology, University of California, 94143-0414, San Francisco, CA, USA;Picobella, LLC, 863 Mitten Road, Suite 101, 94010, Burlingame, CA, USA;

关键词: Benign Prostate Hyperplasia;    Prostate Adenocarcinoma;    Orphan Receptor;    GPR110 Expression;    GPR110 Gene;   

DOI  :  10.1186/1471-2407-10-40

 received in 2008-09-23, accepted in 2010-02-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.MethodsVarious epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.ResultsWe found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.ConclusionOur work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.

【 授权许可】

Unknown   
© Lum et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.