G protein-coupled receptors GPR4 and TDAG8 are oncogenic and overexpressed in human cancers.
The GPR4 subfamily consists of four G protein-coupled receptors that share significant sequence homology. In addition to GPR4, this subfamily includes OGR1, TDAG8 and G2A. G2A has previously been shown to be a potent transforming oncogene for murine 3T3 cells. Here we show that GPR4 also malignantly transforms NIH3T3 cells and that TDAG8 malignantly transforms the normal mammary epithelial cell line NMuMG. Overexpression of GPR4 or TDAG8 in HEK293 cells led to transcriptional activation from SRE- and CRE-driven promoters, independent of exogenously added ligand. TDAG8 and GPR4 are also overexpressed in a range of human cancer tissues. Our results suggest that GPR4 and TDAG8 overexpression in human tumors plays a role in driving or maintaining tumor formation.
Sin
Wun Chey
WC
Genomics Division, Tularik Inc., 266 East Pulaski Rd, Greenlawn, NY 11740, USA.
Zhang
Yaoping
Y
Zhong
Wendy
W
Adhikarakunnathu
Sree
S
Powers
Scott
S
Hoey
Tim
T
An
Songzhu
S
Yang
Jianxin
J
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology*; D015513:Oncogene Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
C091670:GPR4 protein, human; C513334:GPR65 protein, human; C513337:GPR65 protein, mouse; D015513:Oncogene Proteins; D043562:Receptors, G-Protein-Coupled