Artículo

Giacomini, D.; Páez-Pereda, M.; Theodoropoulou, M.; Labeur, M.; Refojo, D.; Gerez, J.; Chervin, A.; Berner, S.; Losa, M.; Buchfelder, M.; Renner, U.; Stalla, G.K.; Arzt, E. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" (2006) Endocrinology. 147(1):247-256
Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease. Copyright © 2006 by The Endocrine Society.

Registro:

Documento: Artículo
Título:Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action
Autor:Giacomini, D.; Páez-Pereda, M.; Theodoropoulou, M.; Labeur, M.; Refojo, D.; Gerez, J.; Chervin, A.; Berner, S.; Losa, M.; Buchfelder, M.; Renner, U.; Stalla, G.K.; Arzt, E.
Filiación:Laboratorio de Fisiología Y Biología Molecular, Departamento de Fisiología, Biología Molecular Y Celular, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Max-Planck Institute of Psychiatry, 80804 Munich, Germany
Hospital Santa Lucía, 1232 Buenos Aires, Argentina
Department of Neurosurgery, Ospedale San Raffaele Instituto di Ricovero e Cura a Carattere Scientifico, 20132 Milan, Italy
Department of Neurosurgery, University of Gottingen Medical School, 37075 Gottingen, Germany
Affectis Pharmaceuticals, 80804 Munich, Germany
Laboratorio de Fisiología Y Biología Molecular, Departemento de Fisiología, Biología Molecular Y Celular, Pabellon II, 1428 Buenos Aires, Argentina
Inst. de Fis., Biologia Molecular Y Neuro Ciencias-Argentine National Research Council (CONICET), Argentina
Palabras clave:bone morphogenetic protein 4; corticotropin; noggin; retinoic acid; Smad4 protein; adenohypophysis; animal cell; animal experiment; animal model; animal tissue; article; cancer inhibition; carcinogenicity; cell line; cell proliferation; comparative study; controlled study; corticotropin release; Cushing disease; disease course; enzyme inhibition; genetic transfection; human; human tissue; mouse; nonhuman; priority journal; protein expression; signal transduction; transcription initiation; Adenoma; Animals; Bone Morphogenetic Proteins; Cell Division; Cell Line, Tumor; Cushing Syndrome; Humans; Immunohistochemistry; Mice; Pituitary Gland; Pituitary Neoplasms; Reference Values; Tretinoin
Año:2006
Volumen:147
Número:1
Página de inicio:247
Página de fin:256
DOI: http://dx.doi.org/10.1210/en.2005-0958
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:Smad4 protein, 282562-18-9; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; retinoic acid, 302-79-4; Bone Morphogenetic Proteins; Tretinoin, 302-79-4; bone morphogenetic protein 4
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00137227_v147_n1_p247_Giacomini.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v147_n1_p247_Giacomini

Referencias:

  • Asa, S.L., Ezzat, S., The cytogenesis and pathogenesis of pituitary adenomas (1998) Endocr Rev, 19, pp. 798-827
  • Yu, R., Melmed, S., Oncogene activation in pituitary tumors (2001) Brain Pathol, 11, pp. 328-341
  • Kovacs, K., Horvath, E., Vidal, S., Classification of pituitary adenomas (2001) J Neurooncol, 54, pp. 121-127
  • Ross, E.J., Linch, D.C., Cushing's syndrome - Killing disease: Discriminatory value of signs and symptoms aiding early diagnosis (1982) Lancet, 2, pp. 646-649
  • Dahia, P.L., Grossman, A.B., The molecular pathogenesis of corticotroph tumors (1999) Endocr Rev, 20, pp. 136-155
  • Wajchenberg, B.L., Mendonca, B.B., Liberman, B., Pereira, M.A., Carneiro, P.C., Wakamatsu, A., Kirschner, M.A., Ectopic adrenocorticotropic hormone syndrome (1994) Endocr Rev, 15, pp. 752-787
  • Alexander, J.M., Biller, B.M., Bikkal, H., Zervas, N.T., Arnold, A., Klibanski, A., Clinically nonfunctioning pituitary tumors are monoclonal in origin (1990) J Clin Invest, 86, pp. 336-340
  • Clayton, R.N., Farrell, W.E., Clonality of pituitary tumours: More complicated than initially envisaged? (2001) Brain Pathol, 11, pp. 313-327
  • Mampalam, T.J., Tyrrell, J.B., Wilson, C.B., Transsphenoidal microsurgery for Cushing disease. A report of 216 cases (1988) Ann Intern Med, 109, pp. 487-493
  • Miller, J.W., Crapo, L., The medical treatment of Cushing's syndrome (1993) Endocr Rev, 14, pp. 443-458
  • Colao, A., Di Sarno, A., Marzullo, P., Di Somma, C., Cerbone, G., Landi, M.L., Faggiano, A., Lombardi, G., New medical approaches in pituitary adenomas (2000) Horm Res, 53 (3 SUPPL.), pp. 76-87
  • Engler, D., Redei, E., Kola, I., The corticotropin-release inhibitory factor hypothesis: A review of the evidence for the existence of inhibitory as well as stimulatory hypophysiotropic regulation of adrenocorticotropin secretion and biosynthesis (1999) Endocr Rev, 20, pp. 460-500
  • Paez-Pereda, M., Kovalovsky, D., Hopfner, U., Theodoropoulou, M., Pagotto, U., Uhl, E., Losa, M., Stalla, G.K., Retinoic acid prevents experimental Cushing syndrome (2001) J Clin Invest, 108, pp. 1123-1131
  • Tran, P., Zhang, X.K., Salbert, G., Hermann, T., Lehmann, J.M., Pfahl, M., COUP orphan receptors are negative regulators of retinoic acid response pathways (1992) Mol Cell Biol, 12, pp. 4666-4676
  • Heaney, A.P., Fernando, M., Yong, W.H., Melmed, S., Functional PPAR-γ receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas (2002) Nat Med, 8, pp. 1281-1287
  • Ray, D., Melmed, S., Pituitary cytokine and growth factor expression and action (1997) Endocr Rev, 18, pp. 206-228
  • Arzt, E., gp130 cytokine signaling in the pituitary gland: A paradigm for cytokine-neuro-endocrine pathways (2001) J Clin Invest, 108, pp. 1729-1733
  • Arzt, E., Pereda, M.P., Castro, C.P., Pagotto, U., Renner, U., Stalla, G.K., Pathophysiological role of the cytokine network in the anterior pituitary gland (1999) Front Neuroendocrinol, 20, pp. 71-95
  • Zafar, M., Ezzat, S., Ramyar, L., Pan, N., Smyth, H.S., Asa, S.L., Cell-specific expression of estrogen receptor in the human pituitary and its adenomas (1995) J Clin Endocrinol Metab, 80, pp. 3621-3627
  • Lieberman, M.E., Maurer, R.A., Claude, P., Wiklund, J., Wertz, N., Gorski, J., Regulation of pituitary growth and prolactin gene expression by estrogen (1981) Adv Exp Med Biol, 138, pp. 151-163
  • Friend, K.E., Chiou, Y.K., Lopes, M.B., Laws Jr., E.R., Hughes, K.M., Shupnik, M.A., Estrogen receptor expression in human pituitary: Correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas (1994) J Clin Endocrinol Metab, 78, pp. 1497-1504
  • Chaidarun, S.S., Eggo, M.C., Stewart, P.M., Barber, P.C., Sheppard, M.C., Role of growth factors and estrogen as modulators of growth, differentiation, and expression of gonadotropin subunit genes in primary cultured sheep pituitary cells (1994) Endocrinology, 134, pp. 935-944
  • Hentges, S., Sarkar, D.K., Transforming growth factor-β regulation of estradiol-induced prolactinomas (2001) Front Neuroendocrinol, 22, pp. 340-363
  • Sheng, H.Z., Moriyama, K., Yamashita, T., Li, H., Potter, S.S., Mahon, K.A., Westphal, H., Multistep control of pituitary organogenesis (1997) Science, 278, pp. 1809-1812
  • Treier, M., Gleiberman, A.S., O'Connell, S.M., Szeto, D.P., McMahon, J.A., McMahon, A.P., Rosenfeld, M.G., Multistep signaling requirements for pituitary organogenesis in vivo (1998) Genes Dev, 12, pp. 1691-1704
  • Paez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grubler, Y., Chervin, A., Arzt, E., Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk (2003) Proc Natl Acad Sci, 100, pp. 1034-1039. , USA
  • Shi, Y., Massague, J., Mechanisms of TGF-β signaling from cell membrane to the nucleus (2003) Cell, 113, pp. 685-700
  • Massague, J., How cells read TGF-β signals (2000) Nat Rev Mol Cell Biol, 1, pp. 169-178
  • Massague, J., Chen, Y.G., Controlling TGF-β signaling (2000) Genes Dev, 14, pp. 627-644
  • Leung, C.K., Paterson, J.A., Imai, Y., Shiu, R.P., Transplantation of ACTH-secreting pituitary tumor cells in athymic nude mice (1982) Virchows Arch A Pathol Anat Histol, 396, pp. 303-312
  • Arzt, E., Stelzer, G., Renner, U., Lange, M., Muller, O.A., Stalla, G.K., Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures (1992) J Clin Invest, 90, pp. 1944-1951
  • Bates, A.S., Farrell, W.E., Bicknell, E.J., McNicol, A.M., Talbot, A.J., Broome, J.C., Perrett, C.W., Clayton, R.N., Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker (1997) J Clin Endocrinol Metab, 82, pp. 818-824
  • Paez Pereda, M., Ledda, M.F., Goldberg, V., Chervin, A., Carrizo, G., Molina, H., Muller, A., Stalla, G.K., High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells (2000) J Clin Endocrinol Metab, 85, pp. 263-269
  • Hata, A., Lagna, G., Massague, J., Hemmati-Brivanlou, A., Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor (1998) Genes Dev, 12, pp. 186-197
  • Monzen, K., Shiojima, I., Hiroi, Y., Kudoh, S., Oka, T., Takimoto, E., Hayashi, D., Komuro, I., Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4 (1999) Mol Cell Biol, 19, pp. 7096-7105
  • Feng, J.Q., Chen, D., Cooney, A.J., Tsai, M.J., Harris, M.A., Tsai, S.Y., Feng, M., Harris, S.E., The mouse bone morphogenetic protein-4 gene. Analysis of promoter utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI orphan receptor (1995) J Biol Chem, 270, pp. 28364-28373
  • Pipaon, C., Tsai, S.Y., Tsai, M.J., COUP-TF upregulates NGFI-A gene expression through an Sp1 binding site (1999) Mol Cell Biol, 19, pp. 2734-2745
  • Takeshita, T., Arita, T., Higuchi, M., Asao, H., Endo, K., Kuroda, H., Tanaka, N., Sugamura, K., STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction (1997) Immunity, 6, pp. 449-457
  • Kovalovsky, D., Refojo, D., Liberman, A.C., Hochbaum, D., Pereda, M.P., Coso, O.A., Stalla, G.K., Arzt, E., Activation and induction of NUR77/NURR1 in corticotrophs by CRH/cAMP: Involvement of calcium, protein kinase A, and MAPK pathways (2002) Mol Endocrinol, 16, pp. 1638-1651
  • Kelloff, G.J., Perspectives on cancer chemoprevention research and drug development (2000) Adv Cancer Res, 78, pp. 199-334
  • Kurie, J.M., The biologic basis for the use of retinoids in cancer prevention and treatment (1999) Curr Opin Oncol, 11, pp. 497-502
  • Lotan, R., Retinoids in cancer chemoprevention (1996) FASEB J, 10, pp. 1031-1039
  • Nudi, M., Ouimette, J.F., Drouin, J., Bone morphogenic protein (Smad)-mediated repression of proopiomelanocortin transcription by interference with Pitx/Tpit activity (2005) Mol Endocrinol, 19, pp. 1329-1342
  • Dasen, J.S., Rosenfeld, M.G., Signaling mechanisms in pituitary morphogenesis and cell fate determination (1999) Curr Opin Cell Biol, 11, pp. 669-677
  • Dasen, J.S., Rosenfeld, M.G., Signaling and transcriptional mechanisms in pituitary development (2001) Annu Rev Neurosci, 24, pp. 327-355
  • Kioussi, C., Carriere, C., Rosenfeld, M.G., A model for the development of the hypothalamic-pituitary axis: Transcribing the hypophysis (1999) Mech Dev, 81, pp. 23-35
  • Ericson, J., Norlin, S., Jessell, T.M., Edlund, T., Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary (1998) Development, 125, pp. 1005-1015
  • Takeda, M., Otsuka, F., Suzuki, J., Kishida, M., Ogura, T., Tamiya, T., Makino, H., Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas (2003) Biochem Biophys Res Commun, 306, pp. 812-818
  • Helvering, L.M., Sharp, R.L., Ou, X., Geiser, A.G., Regulation of the promoters for the human bone morphogenetic protein 2 and 4 genes (2000) Gene, 256, pp. 123-138
  • Kliewer, S.A., Umesono, K., Heyman, R.A., Mangelsdorf, D.J., Dyck, J.A., Evans, R.M., Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling (1992) Proc Natl Acad Sci, 89, pp. 1448-1452. , USA
  • Wu, Q., Li, Y., Liu, R., Agadir, A., Lee, M.O., Liu, Y., Zhang, X., Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization (1997) EMBO J, 16, pp. 1656-1669
  • Beland, M., Lohnes, D., Chicken ovalbumin upstream promoter-transcription factor members repress retinoic acid-induced Cdx1 expression (2005) J Biol Chem, 280, pp. 13858-13862
  • Kang, H.Y., Huang, K.E., Chang, S.Y., Ma, W.L., Lin, W.J., Chang, C., Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4 (2002) J Biol Chem, 277, pp. 43749-43756
  • Matsuda, T., Yamamoto, T., Muraguchi, A., Saatcioglu, F., Cross-talk between transforming growth factor-β and estrogen receptor signaling through Smad3 (2001) J Biol Chem, 276, pp. 42908-42914
  • Sumantran, V.N., Brederlau, A., Funa, K., BMP-6 and retinoic acid synergistically differentiate the IMR-32 human neuroblastoma cells (2003) Anticancer Res, 23, pp. 1297-1303
  • Skillington, J., Choy, L., Derynck, R., Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes (2002) J Cell Biol, 159, pp. 135-146
  • Li, X., Schwarz, E.M., Zuscik, M.J., Rosier, R.N., Ionescu, A.M., Puzas, J.E., Drissi, H., O'Keefe, R.J., Retinoic acid stimulates chondrocyte differentiation and enhances bone morphogenetic protein effects through induction of Smad1 and Smad5 (2003) Endocrinology, 144, pp. 2514-2523
  • Rogers, M.B., Rosen, V., Wozney, J.M., Gudas, L.J., Bone morphogenetic proteins-2 and -4 are involved in the retinoic acid-induced differentiation of embryonal carcinoma cells (1992) Mol Biol Cell, 3, pp. 189-196
  • Rogers, M.B., Receptor-selective retinoids implicate retinoic acid receptor α and γ in the regulation of bmp-2 and bmp-4 in F9 embryonal carcinoma cells (1996) Cell Growth Differ, 7, pp. 115-122
  • Glozak, M.A., Rogers, M.B., Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4 (1996) Dev Biol, 179, pp. 458-470
  • Glozak, M.A., Rogers, M.B., Retinoic acid- and bone morphogenetic protein 4-induced apoptosis in P19 embryonal carcinoma cells requires p27 (2001) Exp Cell Res, 268, pp. 128-138
  • Glozak, M.A., Rogers, M.B., BMP4- and RA-induced apoptosis is mediated through the activation of retinoic acid receptor α and γ in P19 embryonal carcinoma cells (1998) Exp Cell Res, 242, pp. 165-173

Citas:

---------- APA ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., Chervin, A.,..., Arzt, E. (2006) . Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action. Endocrinology, 147(1), 247-256.
http://dx.doi.org/10.1210/en.2005-0958
---------- CHICAGO ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" . Endocrinology 147, no. 1 (2006) : 247-256.
http://dx.doi.org/10.1210/en.2005-0958
---------- MLA ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" . Endocrinology, vol. 147, no. 1, 2006, pp. 247-256.
http://dx.doi.org/10.1210/en.2005-0958
---------- VANCOUVER ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action. Endocrinology. 2006;147(1):247-256.
http://dx.doi.org/10.1210/en.2005-0958