Abstract
To elucidate the function of MAS-related GPCR, member D (MRGD) in cancers, we investigated the in vitro and in vivo oncogenic function of MRGD using murine fibroblast cell line NIH3T3 in which MRGD is stably expressed. The expression pattern of MRGD in clinical samples was also analyzed. We found that overexpression of MRGD in NIH3T3 induced focus formation and multi-cellular spheroid formation, and promoted tumors in nude mice. In other words, overexpression of MRGD in NIH3T3 induced the loss of contact inhibition, anchorage-independent growth and in vivo tumorigenesis. Furthermore, it was found that the ligand of MRGD, beta-alanine, enhanced spheroid formation in MRGD-expressing NIH3T3 cells. From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. Based on these results, MRGD could be involved in tumorigenesis and could also be a novel anticancer drug target.
Highlights
G protein-coupled receptor (GPCR) family members activate various physiological signaling and play an important role in the development as well as function of each organ [1]
Using the NIH3T3-MRGD cells, the focus formation assay was performed, where significant foci formation was seen in the NIH3T3-MRGD cell culture, while no such foci were seen in NIH3T3-Mock (Figure 1A)
We demonstrated that the MRGD expression induces loss of contact inhibition, anchorage-independent spheroid growth in vitro and tumorigenesis in vivo, which are not seen in the parental normal fibroblast cells (Figure 1, Table 1)
Summary
G protein-coupled receptor (GPCR) family members activate various physiological signaling and play an important role in the development as well as function of each organ [1]. High expression of MAS1 was observed in the central nervous system, such as hippocampus and cerebellum, and MAS1 enhanced the ligand-dependent calcium influx of Ang II receptor (AT2R) where MAS1 formed a complex with AT2R. These suggest that MAS1 plays an important role in the central nervous system [7,8]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.