Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer
Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer
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DOI：
10.1186/1471-2407-10-40
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发表时间：
2010-02-11
期刊：
影响因子：
3.8
通讯作者：
Wabl, Matthias
中科院分区：
文献类型：
--
作者：
Lum, Amy M.;Wang, Bruce B.;Wabl, Matthias
背景：GPR110是一种孤儿G蛋白偶联受体--一种没有已知配体、已知信号通路或已知功能的受体。尽管缺乏信息，但人们可以假设孤儿受体具有重要的生物学作用。在小鼠的逆转录病毒插入突变筛选中，我们鉴定了GPR110为癌基因。这促使我们研究从已知的GPR110转录本中收集到的潜在亚型，以及这些亚型在正常和转化的人类组织中的表达。方法：在细胞系中表达各种表位标记的GPR110亚型，并通过Western blotting检测其切割、表面定位和分泌模式。用定量聚合酶链式反应和免疫组织化学方法分别检测了肺癌和前列腺癌细胞系和临床标本中GPR110的转录和蛋白水平。在这些变体中，我们证实有三个是以蛋白质的形式在细胞表面表达的。异构体1为正构型，其分子质量约为100kD。亚型2和3是亚型1的截断产物，分别为25kD和23kD。这些截短的异构体缺乏GPR蛋白的七跨膜结构域特征，因此不太可能是膜锚定的；实际上，异构体2可以分泌。与选择的200个相似基因的中位数相比，GPR110在大多数组织中的表达水平较低。然而，它在正常肾组织和来自老年捐赠者的前列腺组织中的基因表达高于平均水平。尽管GPR110被确认为小鼠T淋巴瘤的癌基因，但它在人类肺癌和前列腺癌中大量过度表达。免疫组织化学检测GPR110在27个肺腺癌组织核心中高表达20个(74%)，在29个前列腺癌组织核心中高表达17个(59%)。此外，GPR110抗体染色使我们能够区分良性前列腺增生症和潜在的早期恶性肿瘤。结论：我们的工作表明GPR110在肿瘤生理学中的作用，并支持它作为肺癌和前列腺癌的潜在候选治疗和疾病标记物。
Background: GPR110 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.Methods: Various 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.Results: We 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 similar to 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.Conclusion: Our 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.