Transcriptional activation of the human gastrin-releasing peptide receptor gene in gastrointestinal and prostatic epithelial cancer cells.
The mammalian gastrin-releasing peptide receptor (GRP-R) belongs to the superfamily of G protein-coupled receptors and mediates actions of the regulatory GRP and bombesin, the amphibian homolog of GRP. Owing to its frequent ectopic expression in some epithelial human malignancies, such as cancers of the colon, lung, and prostate, ligand-specific receptor activation may initiate intracellular signals of cell proliferation, differentiation and migration in this context. Because the underlying molecular mechanisms of aberrant human GRP-R (hGRP-R) expression in tumorigenesis remain unknown, we examined in this study the transcriptional activation of hGRP-R in gastrointestinal and prostate cancer cells, which natively express functional hGRP-R. Using various hGRP-R promoter mutants cloned into a luciferase reporter plasmid, transient transfection studies demonstrated robust transcriptional activation in gastrointestinal and prostate cancer cells. Although our study revealed distinct patterns of transcriptional hGRP-R activation in gastrointestinal and prostate cancer cells, genomic sequences between 97 and 247 bp upstream of the major RNA initiation site appear to be of particular significance for basal transcriptional hGRP-R activation. Based on this study, future examination of transcription factor interaction with the hGRP-R promoter will be important to identify molecular mechanisms of hGRP-R regulation relevant in human cancers that express functional receptor sites
Qu
Xiangping
X
Section of Gastroenterology, Boston University School of Medicine, Boston, MA 02118, USA.
Xiao
Dongmei
D
Weber
H Christian
HC
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008156:Luciferases; D008297:Male; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018004:Receptors, Bombesin / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D008156:Luciferases