Transcriptional activation of the human gastrin-releasing peptide receptor gene in gastrointestinal and prostatic epithelial cancer cells
- 56 Downloads
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.
Index EntriesRegulatory peptide bombesin gene regulation GRP-R cancer
Unable to display preview. Download preview PDF.
- Centers for Disease Control and Prevention (2002) Recent trends in mortality rates for four major cancers, by sex and race/ethnicity—United States, 1990–1998. MMWR Morb. Mortal. Wkly. Rep. 51, 49–53.Google Scholar
- Bokar, J. A., Roesler, W. J., Vandenbark, G. R., Kaetzel, D. M., Hanson, R. W., and Nilson, J. H. (1988) Characterization of the cAMP responsive elements from the genes for the alpha-subunit of glycoprotein hormones and phosphoenolpyruvate carboxykinase (GTP). Conserved features of nuclear protein binding between tissues and species. J. Biol. Chem. 263, 19740–19747.PubMedGoogle Scholar
- Qu, X., Xiao, D., and Weber, H. C. (2003a) Protein kinase A (PKA)-induced GRP-receptor (hGRP-R) regulation requires transcription factor binding at two distinct CRE sites. Gastroenterology 124, A9.Google Scholar
- Reile, H., Armatis, P. E., and Schally, A. V. (1994) Characterization of high-affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC-3 and DU-145: internalization of receptor bound 125I-(Tyr4) bombesin by tumor cells. Prostate 25, 29–38.PubMedCrossRefGoogle Scholar
- Schug, J. and Overton, G.C. (1997) TESS: Transcription Element Search Software on the WWW. Technical Report CBIL-TR-1997-1001-v0.0, Computational Biology and Informatics Laboratory, http://www.cbil.upenn.edu/tess. School of Medicine, University of Pennsylvania, 1997.Google Scholar
- Weber, H. C., Battey, J. F., and Jensen, R. T. (1997) A cyclic AMP response element (CRE) in the murine GRP-R promoter is necessary for basal transcription activity. Gastroenterology 112, A1199.Google Scholar
- Weber, H. C., Hampton, L. L., Jensen, R. T., and Battey, J. F. (1996) Structure and chromosomal localization of the genes for the gastrin-releasing peptide receptor, neuromedin-B receptor and the bombesin suptype 3 receptor. Regul. Peptides 64, 207.Google Scholar