Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors
Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors
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DOI：
10.4161/cbt.5.4.2521
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Samatar, Ahmed A.
中科院分区：
文献类型：
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作者：
McClanahan, Terrill;Koseoglu, Sandra;Samatar, Ahmed A.
我们使用基因表达谱来探测15组结肠肿瘤和匹配的正常结肠组织之间转录输出的差异。该分析显示，与正常结肠组织相比，GPRA 9（孤儿G蛋白偶联受体（GPCR））在66%（10115）的结肠肿瘤中过表达。随后通过实时定量逆转录酶对另外39组匹配的正常和肿瘤结肠组织进行分析，证实了该受体的上调。GPR 49在正常组织和肿瘤组织中的表达差异有显著性（p > 0.001）。GPR 49在39个结肠原发性肿瘤组织中的25个（64%）中上调。除了结肠肿瘤，还发现GPRA 9在通过RT-PCR分析的33个卵巢原发性肿瘤组织中的18个（53%）中上调。此外，GPRA 9在结肠和卵巢肿瘤中的表达水平在更晚期的肿瘤中增加，表明受体在肿瘤进展中的作用。通过结肠和卵巢肿瘤组织的特异性免疫组织化学染色进一步说明肿瘤组织中GPR 49的选择性过表达，这一发现与受体的mRNA表达相关。此外，GPRA 9的表达以配体依赖性方式诱导转化，GPR 49 mRNA水平的敲低诱导结肠肿瘤细胞的凋亡。这些新的发现为进一步的研究提供了基础，并表明GPR 49在肿瘤发生中的潜在作用。
We used gene expression profiling to probe differences in transcriptional output between 15 panels of colon tumor and matched normal colon tissues. This analysis revealed that GPRA9, an orphan G Protein-Coupled Receptor (GPCR) is overexpressed in 66% (10115) colon tumors compared with normal colon tissues. Subsequent analysis of an additional 39 sets of matched normal and tumor colon tissues by real-time quantitative reverse transcriptase confirmed the upregulation of this receptor. The differential expression of GPR49 between normal and tumor tissue was significant (p > 0.001). GPR49 was upregulated in 25 of 39 (64%) colon primary tumor tissues. In addition to colon tumors, GPRA9 was also found to be upregulated in 18 of 33 (53%) ovarian primary tumor tissues analyzed by RT-PCR. Moreover, the expression level of GPRA9 in colon and ovarian tumors increased in more advanced tumors suggesting a role for the receptor in tumor progression. The selective overexpression of GPR49 in tumor tissues was further illustrated by specific immunohistochemical staining of colon and ovarian tumor tissues, a finding that correlates with the mRNA expression of the receptor. In addition, expression of GPRA9 induced transformation in a ligand-dependent manner and Knockdown of GPR49 mRNA level induced apoptosis in colon tumor cells. These novel findings provide a foundation for further studies and suggest a potential role for GPR49 in tumorigenesis.