Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors.
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 GPR49, an orphan G Protein-Coupled Receptor (GPCR) is overexpressed in 66% (10/15) 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, GPR49 was also found to be upregulated in 18 of 33 (53%) ovarian primary tumor tissues analyzed by RT-PCR. Moreover, the expression level of GPR49 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 GPR49 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.
DNAX Research Institute, Schering-Plough Research Institute, Kenilworth, New Jersey 07333, USA.
Terrill
T
McClanahan
Sandra
S
Koseoglu
Kathleen
K
Smith
Jeffrey
J
Grein
Eric
E
Gustafson
Stuart
S
Black
Paul
P
Kirschmeier
Ahmed A
AA
Samatar
D017209:Apoptosis; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C116884:LGR5 protein, human; D008024:Ligands; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled