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Differential Somatostatin Receptor Subtype Expression in Human Normal Pineal Gland and Pineal Parenchymal Tumors

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Abstract

Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase–polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1–sst5). Pineal parenchymal tumor (PTT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtype sst2, evidenced an about sixfold higher level in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.

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References

  • Baou, N., Bouras, M., Droz, J. P., Benhamed, M., and Krantic, S. (2000). Evidence for a selective loss of somatostatin receptor subtype expression in male germ tumors of seminoma type. Carcinogenesis 21:805–810.

    Google Scholar 

  • Boularand, S., Darmon, M. C, and Mallet, J. (1995). The human tryptophan hydroxylase gene. An unusual splicing complexity in the 5′-untranslated region. J. Biol. Chem. 270:3748–3756.

    Google Scholar 

  • Bruggers, C. S., Tai, K. F., Murdock, T., Sivak, L., Le, K., Perkins, S. L., Coffin, C. M., and Caroll, W. L. (1998). Expression of the c-myc protein in childhood medulloblastoma. J. Pediat. Hematol. Oncol. 20:18–25.

    Google Scholar 

  • Bruno, J. F., Xu, Y., Song, J., and Berelowitz, M. (1992). Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc. Natl. Acad. Sci. U.S.A. 89:4618–4622.

    Google Scholar 

  • Buscail, L., Esteve, J., Saint-Laurent, N., Bertrand, V., Reisine, T., O'Carroll, A., Bell, G., Schally, A., Vayssen, N., and Susini, C. (1995). Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc. Natl. Acad. Sci. U.S.A. 92:1580–1584.

    Google Scholar 

  • Buscail, L., Saint-Laurent, N., Chastre, E., Vaillant, J. C., Gespach, C., Capella, G., Kalthoff, H., Lluis, F., Vaysse, N., and Susini, C. (1996). Loss of somatostatin receptor gene expression in human pancreatic and colorectal cancer. Cancer Res. 56:1823–1827.

    Google Scholar 

  • Casini Raggi, C., Calabro, A., Renzi, D., Briganti, V., Cianchi, F., Messerini, L., Valanzano, R., Smith, M. C., Cortesini, C., Tonelli, F., Serio, M., Maggi, M., and Orlando, C. (2002). Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa. Clin. Cancer Res. 8:419–427.

    Google Scholar 

  • Chomczynski, P., and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–159.

    Google Scholar 

  • Coon, S. L., Mazuruk, K., Bernard, M., Roseboom, P. H., Klein, D. C., and Rodriguez, R. (1996). The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization and tissue expression. Genomics 34:76–84.

    Google Scholar 

  • Csaba, Z., and Dournaud, P. (2001). Cellular biology of somatostatin receptors. Neuropeptides 35:1–23.

    Google Scholar 

  • Debus, N., Dutour, A., Vuaroqueaux, V., Oliver, C., and Ouafik, L. H. (2001). The ovine somatostatin receptor subtype 1 (osst1): Partial cloning and tissue distribution. Domest. Anim. Endocrinol. 21:73–84.

    Google Scholar 

  • Delesque, N., Buscail, L., Esteve, J. P., Saint-Laurent, N., Muller, C., Weckbecker, G., Bruns, C., Vayssen, N., and Susini, C. (1997). Sst2 somatostatin receptor expression reverses tumorigenecity of human pancreatic cancer cells. Cancer Res. 57:956–962.

    Google Scholar 

  • Evans, A. A., Crook, T., Laws, S. A. M., Gough, A. C., Royle, G. T., and Primorse, J. N. (1997). Analysis of somatostatin receptor subtype mRNA expression in human breast cancer. Br. J. Cancer 75:798–803.

    Google Scholar 

  • Fevre-Montange, M., Jouvet, A., Privat, K., Korf, H. W., Champier, J., Reboul, A., Aguera, C., and Mottolese, C. (1998). Immunohistochemical, ultrastructural, biochemical and in vitro studies of a pineocytoma. Acta Neuropathol. (Berl.) 95:532–539.

    Google Scholar 

  • Fodor, M., Slama, A., Guillaume, V., Csaba, Z., Oliver, C., and Epelbaum, J. (1997). Distribution and pharmacological characterization of somatostatin receptor binding sites in the sheep brain. J. Chem. Neuroanat. 12:175–182.

    Google Scholar 

  • Guyotat, J., Champier, J., Jouvet, A., Signorelli, F., Houzard, C., Bret, P., Saint-Pierre, G., and Fevre-Montange, M. (2001a). Differential expression of somatostatin receptors in ependymoma, implications for diagnosis. Int. J. Cancer 95:145–151.

    Google Scholar 

  • Guyotat, J., Champier, J., Saint-Pierre, G., Jouvet, A., Bret, P., Brisson, C., Belin, M. F., Signorelli, F., and Fevre-Montange, M. (2001b). Differential expression of somatostatin receptors in medulloblastoma. J. Neuro-Oncol. 51:93–103.

    Google Scholar 

  • Hofland, L. J., and Lamberts, S. W. J. (2001). Somatostatin receptor subtype expression in human tumors. Ann. Oncol. 12:S31-S36.

    Google Scholar 

  • Hofland, L. J., Liu, Q., Van Koetsveld, P. M., Zuijderwijk, J., Van Der Ham, F., De Krijger, R. R., Schonbrunn, A., and Lamberts, S. W. J. (1999). Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2 in human somatostatin receptor positive tumors. J. Clin. Endocrinol. Metab. 84:775–780.

    Google Scholar 

  • Hoyer, D., Bell, G. I., Berelowitz, M., Epelbaum, J., Feniuk, W., Humphrey, P. P. A., O'Caroll, A. M., Patel, Y. C., Schonbrunn, A., Taylor, J. E., and Reisine, T. (1995). Classification and nomenclature of somatostatin receptors. Trends Pharmacol. Sci. 16:86–88.

    Google Scholar 

  • Jouvet, A., Fevre-Montange, M., Besançon, R., Derrington, E., Saint-Pierre, G., Belin, M. F., Pialat, J., and Lapras, C. (1994). Structural and ultrastructural characteristics of human pineal gland and pineal parenchymal tumors. Acta Neuropathol. 88:334–348.

    Google Scholar 

  • Jouvet, A., Saint-Pierre, G., Fauchon, F., Privat, K., Bouffet, E., Ruchoux, M. M., Chauveinc, L., and Fevre-Montange, M. (2000). Pineal parenchymal tumors: A correlation of histological features with prognosis in 66 cases. Brain Pathol. 10:49–60.

    Google Scholar 

  • Kees, U. R., Spagnolo, D., Hallam, L. A., Ford, J., Ranford, P. R., Baker, D. L., Callen, D. F., and Biegel, J. A. (1998). A new pineoblastoma cell line, PER-480, with der(10)t(1;16), der(16)t(1;17), and enhanced MYC expression in the absence of gene amplification. Cancer Genet. Cytogenet. 100:159–164.

    Google Scholar 

  • Komatsuzaki, K., Terashita, K., Kinane, T. B., and Nishimoto, I. (2001). Somatostatin type V receptor activates c-jun N-terminal kinases via Gα12 family G proteins. Biochem. Biophys. Res. Commun. 289:1211–1217.

    Google Scholar 

  • Lew, G. M., and Lawson-Willey, A. (1987). An immunohistochemical study in the ovine, porcine and rodent pineal gland. Histochemistry 86:591–593.

    Google Scholar 

  • Mato, E., Matias-Guiu, X., Chico, A., Webb, S. M., Cabezas, R., Berna, L., and De Leiva, A. (1998). Somatostatin and somatostatin receptor subtype gene expression in medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 83:2417–2420.

    Google Scholar 

  • Mato, E., Santisteban, P., Chowen, J. A., Fornas, O., Bouwens, M., Puig-Domingo, M., Argente, J., and Webb, S. (1997). Circannual somatostatin gene and somatostatin receptor gene expression in the early post-natal rat pineal gland. Neuroendocrinology 66:368–374.

    Google Scholar 

  • Mato, E., Santisteban, P., Viader, M., Capella, G., Fornas, O., Puig-Domingo, M., and Webb, S. M. (1993). Expression of somatostatin in rat pineal cells in culture. J. Pineal Res. 15:43–45.

    Google Scholar 

  • Patel, Y. C. (1999). Somatostatin and its receptor family. Front. Neuroendocrinol. 20:157–198.

    Google Scholar 

  • Patel, Y. C., Rao, K., and Reichlin, S. (1977). Somatostatin in human cerebrospinal fluid. N. Engl. J. Med. 296:529–533.

    Google Scholar 

  • Peinado, M. A., Viader, M., Puig-Domingo, M., Hernandez, G., Reiter, R. J., and Webb, S. M. (1989). Regional distribution of immunoreactive somatostatin in the bovine pineal gland. Neuroendocrinology 50:550–554.

    Google Scholar 

  • Pelletier, G., Leclerc, R., Dube, D., Labrie, F., Buvani, R., Arimura, A., and Schally, A. V. (1975). Localization of growth-hormone release inhibiting hormone (somatostatin) in the rat brain. Am. J. Anat. 42:397–400.

    Google Scholar 

  • Przybylska-Gornowicz, B., Helboe, L., Lewczuk, B., and Moller, M. (2000). Somatostatin and somatostatin receptors in the pig pineal gland during postnatal development: An immunocytochemical study. Anat. Rec. 259:141–149.

    Google Scholar 

  • Rodriguez, I. R., Mazuruk, K., Schoen, T. J., and Chader, G. J. (1994). Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters. J. Biol. Chem. 269:31969–31977.

    Google Scholar 

  • Sabry, I., and Suzuki, M. (1993). Immunoreactive somatostatin content in the pineal gland increases after lesion of the hypothalamic periventricular nucleus in male rats. J. Pineal Res. 14:23–26.

    Google Scholar 

  • Schindler, M., Holloway, S., Humphrey, P. P. A., Waldvogel, H., Faull, R. L. M., Berger, W., and Emson, P. C. (1998). Localization of the somatostatin SST2A receptor in human cerebral cortex, hippocampus and cerebellum. Neuroreport 9:521–525.

    Google Scholar 

  • Schulz, S., Handel, M., Schreff, M., Schmidt, H., and Hollt, V. (2000). Localization of five somatostatin receptors in the rat central nervous system using subtype-specific antibodies. J. Physiol. Paris 94:259–264.

    Google Scholar 

  • Selmer, I. S., Schindler, M., Humphrey, P. P. A., Waldvogel, H. J., Faull R. L. M., and Emson, P. C. (2000). First localisation of somatostatin sst4 receptor protein in selected human brain areas: An immunohistochemical study. Mol. Brain Res. 82:114–125.

    Google Scholar 

  • Sugden, D., and Klein, D. C. (1987). Inactivation of rat pineal hydroxyindol-O-methyltransferase by disulfite-containing peptides: Insulin is the most potent. J. Biol. Chem. 262:6489–6493.

    Google Scholar 

  • Thoss, V. S., Perez, J., Probat, A., and Hoyer, D. (1996). Expression of five somatostatin receptor mRNAs in the human brain and pituitary. Arch. Pharmacol. 354:411–419.

    Google Scholar 

  • Tsumanuma, I., Tanaka, R., Ichikawa, T., Washiyama, K., and Kumanishi, T. (2000). Demonstration of hydroxyindole-O-methyltransferase (HIOMT) mRNA expression in pineal parenchymal tumors: Histochemical in situ hybridization. J. Pineal Res. 28:203–209.

    Google Scholar 

  • Webb, S., Lewinski, A. K., and Reiter, R. J. (1985). Somatostatin: Its possible relevance to pineal function In: Reiter, R. J., and Liss, A. R. (eds), Pineal Research Reviews, New York, pp. 215–236.

  • Yamada, Y., Post, S. R., Wang, K., Tager, H. S., Bell, G. I., and Seino, S. (1992). Somatostatin receptors, an expanding gene family: Cloning and functional characterization of human SSRT3, a protein coupled to adenylyl cyclase. Mol. Endocrinol. 6:2136–2141.

    Google Scholar 

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Champier, J., Jouvet, A., Rey, C. et al. Differential Somatostatin Receptor Subtype Expression in Human Normal Pineal Gland and Pineal Parenchymal Tumors. Cell Mol Neurobiol 23, 101–113 (2003). https://doi.org/10.1023/A:1022549218902

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