Abstract
Gastrin-releasing peptide (GRP) is considered to be one of the cancer growth factors. This peptide’s receptor (GRPR) is known as a G protein-coupled receptor, regulating intracellular calcium storage and releasing signals. This study is the first to investigate the function of GRP during mouse incisor development. We hypothesized that GRP is one of the factors that affects the regulation of calcification during tooth development. To verify the expression pattern of GRP, in situ hybridization was processed during incisor development. GRP was expressed at the late bell stage and hard tissue formation stage in the epithelial tissue. To identify the genuine function of GRP during incisor development, a gain-of-function analysis was performed. After GRP overexpression in culture, the phenotype of ameloblasts, odontoblasts and predentin was altered compared to control group. Moreover, enamel and dentin thickness was increased after renal capsule transplantation of GRP-overexpressed incisors. With these results, we suggest that GRP plays a significant role in the formation of enamel and dentin by regulating ameloblasts and predentin formation, respectively. Thus, GRP signaling is strongly related to calcium acquisition and secretion during mouse incisor development.
Similar content being viewed by others
References
Aprikian AG, Han K, Chevalier S, Bazinet M, Viallet J (1996) Bombesin specifically induces intracellular calcium mobilization via gastrin-releasing peptide receptors in human prostate cancer cells. J Mol Endocrinol 16(3):297–306
Benya RV, Kusui T, Pradhan TK, Battey JF, Jensen RT (1995) Expression and characterization of cloned human bombesin receptors. Mol Pharmacol 47(1):10–20
Chen J, Zhou JH, Mokotoff M, Fanger MW, Ball ED (1995) Lysis of small cell carcinoma of the lung (SCCL) cells by cytokine-activated monocytes and natural killer cells in the presence of bispecific immunoconjugates containing a gastrin-releasing peptide (GRP) Analog or a GRP Antagonist. J Hematother 4(5):369–376
Chinnappan D, Qu X, Xiao D, Ratnasari A, Weber HC (2008) Human gastrin-releasing peptide receptor gene regulation requires transcription factor binding at two distinct CRE sites. Am J Physiol Gastrointest Liver Physiol 295(1):G153–G162
Flores D, Lenz G, Roesler R, Schwartsmann G (2009) Gastrin-releasing peptide receptor signaling in cancer. Cancer Therapy 7:331–345
Karlsson S, Ahrén B (1996) Gastrin-releasing peptide mobilizes calcium from intracellular stores in HIT-T15 cells. Peptides 17(6):909–916
Mansi R, Fleischmann A, Mäcke HR, Reubi JC (2013) Targeting GRPR in urological cancers—from basic research to clinical application. Nat Rev Urol 10:235–244
Mansi R, Abiraj K, Wang X, Tamma ML, Gourni E, Cescato R, Berndt S, Reubi JC, Maecke HR (2015) Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors. J Med Chem 58(2):682–691
Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59:1152–1159
Nebgen DR, Inoue H, Sabsay B, Wei K, Ho C-S, Veis A (1999) Identification of the chondrogenic inducing activity from bovine dentin (bCIA) as a low molecular mass amelogenin polypeptide. J Dent Res 78:1484–1494
Qiao J, Kang JH, Cree J, Evers M, Chung DH (2005) Gastrin-releasing peptide-induced down-regulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten) in neuroblastomas. Ann Surg 241(5):684–692
Snead M, Luo W, Lau E, Slavkin H (1988) Spatial- and temporal-restricted pattern for amelogenin gene expression during mouse molar tooth organogenesis. Development 104:77–85
Solorzano C, Villafuerte D, Meda K, Cevikbas F, Bráz J, Sharif-Naeini R, Juarez-Salinas D, Llewellyn-Smith IJ, Guan Z, Basbaum AI (2015) Primary afferent and spinal cord expression of gastrin-releasing peptide: message, protein, and antibody concerns. J Neurosci 35(2):648–657
Squires P, Meloche R, Buchan A (1999) Bombesin-evoked gastrin release and calcium signaling in human antral G cells in culture. Am J Physiol Gastrointest Liver Physiol 276(39):G227–G237
Takahashi T, Machida K, Honda N, Hosono M, Oku S, Osada H, Murata O, Nishimura K, Ohno H (2004) Extraosseous accumulation of 99mTc-MDP in lymph node metastases of small cell carcinoma of the esophagus. Ann Nucl Med 18(2):157–160
Uchida K, Kojima A, Morokawa N, Tanabe O, Anzai C, Kawakami M, Eto Y, Yoshimura K (2003) Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer. J Cancer Res Clin Oncol 128(12):633–640
Veis A, Tompkins K, Alvares K, Wei K, Wang L, Wang XS et al (2000) Specific amelogenin gene splice products have signaling effects on cells in culture and implant in vivo. J Biol Chem 275:41263–41272
Acknowledgments
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3266). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI14C1817).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Jong-Min Lee and Han-Sung Jung have contributed equally in this work.
Rights and permissions
About this article
Cite this article
Lee, DJ., Jin, C., Kim, EJ. et al. Gastrin-releasing peptide expression and its effect on the calcification of developing mouse incisor. Histochem Cell Biol 144, 273–279 (2015). https://doi.org/10.1007/s00418-015-1335-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-015-1335-1