Navegar

Colección

Datos Estadísticas

Artículo

Fuertes, M.; Sapochnik, M.; Tedesco, L.; Senin, S.; Attorresi, A.; Ajler, P.; Carrizo, G.; Cervio, A.; Sevlever, G.; Bonfiglio, J.J.; Stalla, G.K.; Arzt, E. "Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity" (2018) Endocrine-Related Cancer. 25(6):665-676
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Increased levels of the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) have been repeatedly reported in several human solid tumors, especially in endocrine-related tumors such as pituitary adenomas. Securin PTTG has a critical role in pituitary tumorigenesis. However, the cause of upregulation has not been found yet, despite analyses made at the gene, promoter and mRNA level that show that no mutations, epigenetic modifications or other mechanisms that deregulate its expression may explain its overexpression and action as an oncogene. We describe that high PTTG protein levels are induced by the RWD-containing sumoylation enhancer (RWDD3 or RSUME), a protein originally identified in the same pituitary tumor cell line in which PTTG was also cloned. We demonstrate that PTTG and RSUME have a positive expression correlation in human pituitary adenomas. RSUME increases PTTG protein in pituitary tumor cell lines, prolongs the half-life of PTTG protein and regulates the PTTG induction by estradiol. As a consequence, RSUME enhances PTTG transcription factor and securin activities. PTTG hyperactivity on the cell cycle resulted in recurrent and unequal divisions without cytokinesis, and the consequential appearance of aneuploidies and multinucleated cells in the tumor. RSUME knockdown diminishes securin PTTG and reduces its tumorigenic potential in a xenograft mouse model. Taken together, our findings show that PTTG high protein steady state levels account for PTTG tumor abundance and demonstrate a critical role of RSUME in this process in pituitary tumor cells. © 2018 Society for Endocrinology.

Registro:

Documento: Artículo
Título:Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity
Autor:Fuertes, M.; Sapochnik, M.; Tedesco, L.; Senin, S.; Attorresi, A.; Ajler, P.; Carrizo, G.; Cervio, A.; Sevlever, G.; Bonfiglio, J.J.; Stalla, G.K.; Arzt, E.
Filiación:Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Servicio de Neurocirugía, Hospital Italiano, Buenos Aires, Argentina
Departamento de Neurocirugía, Fundación para la Lucha Contra Las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina
Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany
Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Pituitary tumors; PTTG; RSUME; pituitary tumor transforming gene; protein; securin; transcription factor; unclassified drug; aneuploidy; animal cell; Article; carcinogenicity; cell cycle; controlled study; hypophysis adenoma; hypophysis tumor; male; mouse; mouse model; multinuclear cell; nonhuman; pituitary tumor cell line; protein stability; steady state; sumoylation; tumor xenograft
Año:2018
Volumen:25
Número:6
Página de inicio:665
Página de fin:676
DOI: http://dx.doi.org/10.1530/ERC-18-0028
Título revista:Endocrine-Related Cancer
Título revista abreviado:Endocr.-Relat. Cancer
ISSN:13510088
CODEN:ERCAE
CAS:protein, 67254-75-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13510088_v25_n6_p665_Fuertes

Referencias:

  • Amousha, M.R., Sabetkish, N.S., Heshmat, R., Rajabiani, A., Saffar, H., Haghpanah, V., Tavangar, S.M., Expression of the Pituitary Tumor Transforming Gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors (2015) Acta Medica Iranica, 53, pp. 236-241
  • 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) Frontiers in Neuroendocrinology, 20, pp. 71-95. , https://doi.org/10.1006/frne.1998.0176
  • Beckers, A., Higher prevalence of clinically relevant pituitary adenomas confirmed (2010) Clinical Endocrinology, 72, pp. 290-291. , https://doi.org/10.1111/j.1365-2265.2009.03726.x
  • Boelaert, K., McCabe, C.J., Tannahill, L.A., Gittoes, N.J., Holder, R.L., Watkinson, J.C., Bradwell, A.R., Franklyn, J.A., Pituitary tumor transforming gene and fibroblast growth factor-2 expression: Potential prognostic indicators in differentiated thyroid cancer (2003) Journal of Clinical Endocrinology and Metabolism, 88, pp. 2341-2347. , https://doi.org/10.1210/jc.2002-021113
  • Boggio, R., Colombo, R., Hay, R.T., Draetta, G.F., Chiocca, S., A mechanism for inhibiting the SUMO pathway (2004) Molecular Cell, 16, pp. 549-561. , https://doi.org/10.1016/j.molcel.2004.11.007
  • Comprehensive molecular characterization of clear cell renal cell carcinoma (2003) Nature, 499, pp. 43-49. , https://doi.org/10.1038/nature12222
  • Carbia-Nagashima, A., Gerez, J., Perez-Castro, C., Paez-Pereda, M., Silberstein, S., Stalla, G.K., Holsboer, F., Arzt, E., RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia (2007) Cell, 131, pp. 309-323. , https://doi.org/10.1016/j.cell.2007.07.044
  • Castro, C.P., Giacomini, D., Nagashima, A.C., Onofri, C., Graciarena, M., Kobayashi, K., Paez-Pereda, M., Arzt, E., Reduced expression of the cytokine transducer gp130 inhibits hormone secretion, cell growth, and tumor development of pituitary lactosomatotrophic GH3 cells (2003) Endocrinology, 144, pp. 693-700. , https://doi.org/10.1210/en.2002-220891
  • Ciechanover, A., The ubiquitin-proteasome proteolytic pathway (1994) Cell, 79, pp. 13-21. , https://doi.org/10.1016/0092-8674(94)90396-4
  • Clayton, R.N., Farrell, W.E., Pituitary tumour clonality revisited (2004) Frontiers of Hormone Research, 32, pp. 186-204
  • Chesnokova, V., Zonis, S., Rubinek, T., Yu, R., Ben-Shlomo, A., Kovacs, K., Wawrowsky, K., Melmed, S., Senescence mediates pituitary hypoplasia and restrains pituitary tumor growth (2007) Cancer Research, 67, pp. 10564-10572. , https://doi.org/10.1158/0008-5472.CAN-07-0974
  • Chesnokova, V., Zonis, S., Kovacs, K., Ben-Shlomo, A., Wawrowsky, K., Bannykh, S., Melmed, S., P21(Cip1) restrains pituitary tumor growth (2008) PNAS, 105, pp. 17498-17503. , https://doi.org/10.1073/pnas.0804810105
  • Dominguez, A., Ramos-Morales, F., Romero, F., Rios, R.M., Dreyfus, F., Tortolero, M., Pintor-Toro, J.A., Hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG (1998) Oncogene, 17, pp. 2187-2193. , https://doi.org/10.1038/sj.onc.1202140
  • Drouin, J., Bilodeau, S., Roussel-Gervais, A., Stem cells, differentiation and cell cycle control in pituitary (2010) Frontiers of Hormone Research, 38, pp. 15-24
  • Druker, J., Liberman, A.C., Antunica-Noguerol, M., Gerez, J., Paez-Pereda, M., Rein, T., Iniguez-Lluhi, J.A., Arzt, E., RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity (2013) Molecular and Cellular Biology, 33, pp. 2116-2127. , https://doi.org/10.1128/MCB.01470-12
  • Dworakowska, D., Grossman, A.B., The molecular pathogenesis of pituitary tumors: Implications for clinical management (2012) Minerva Endocrinologica, 37, pp. 157-172
  • Farrell, W.E., Epigenetics of pituitary tumours: An update (2014) Current Opinion in Endocrinology, Diabetes and Obesity, 21, pp. 299-305. , https://doi.org/10.1097/MED.0000000000000078
  • Fernandez, A., Karavitaki, N., Wass, J.A., Prevalence of pituitary adenomas: A community-based, cross-sectional study in Banbury (Oxfordshire, UK) (2010) Clinical Endocrinology, 72, pp. 377-382. , https://doi.org/10.1111/j.1365-2265.2009.03667.x
  • Fowkes, R.C., Vlotides, G., Hypoxia-induced VEGF production 'RSUMEs' in pituitary adenomas (2012) Endocrine-Related Cancer, 19, pp. C1-C5. , https://doi.org/10.1530/ERC-11-0297
  • Gao, J., Aksoy, B.A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S.O., Sun, Y., Larsson, E., Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal (2013) Science Signaling, 6, p. 11
  • Gatto, F., Feelders, R., Van Der Pas, R., Kros, J.M., Dogan, F., Van Koetsveld, P.M., Van Der Lelij, A.J., De Herder, W., Beta- Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: Role in the regulation of response to somatostatin analogue treatment in patients with acromegaly (2013) Endocrinology, 154, pp. 4715-4725. , https://doi.org/10.1210/en.2013-1672
  • Geiss-Friedlander, R., Melchior, F., Concepts in sumoylation: A decade on (2007) Nature Reviews Molecular Cell Biology, 8, pp. 947-956. , https://doi.org/10.1038/nrm2293
  • Genkai, N., Homma, J., Sano, M., Tanaka, R., Yamanaka, R., Increased expression of pituitary tumor-transforming gene (PTTG)-1 is correlated with poor prognosis in glioma patients (2006) Oncology Reports, 15, pp. 1569-1574
  • Gerez, J., Fuertes, M., Tedesco, L., Silberstein, S., Sevlever, G., Paez-Pereda, M., Holsboer, F., Arzt, E., In silico structural and functional characterization of the RSUME splice variants (2013) PLoS ONE, 8, p. e57795. , https://doi.org/10.1371/journal.pone.0057795
  • Gerez, J., Tedesco, L., Bonfiglio, J.J., Fuertes, M., Barontini, M., Silberstein, S., Wu, Y., Holsboer, F., RSUME inhibits VHL and regulates its tumor suppressor function (2015) Oncogene, 34, pp. 4855-4866. , https://doi.org/10.1038/onc.2014.407
  • Hay, R.T., SUMO: A history of modification (2005) Molecular Cell, 18, pp. 1-12. , https://doi.org/10.1016/j.molcel.2005.03.012
  • He, W., Huang, L., Shen, X., Yang, Y., Wang, D., Zhu, X., Relationship between RSUME and HIF-1alpha/VEGF-A with invasion of pituitary adenoma (2017) Gene, 603, pp. 54-60. , https://doi.org/10.1016/j.gene.2016.12.012
  • Heaney, A.P., Horwitz, G.A., Wang, Z., Singson, R., Melmed, S., Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis (1999) Nature Medicine, 5, pp. 1317-1321. , https://doi.org/10.1038/15275
  • Heaney, A.P., Singson, R., McCabe, C.J., Nelson, V., Nakashima, M., Melmed, S., Expression of pituitary-tumour transforming gene in colorectal tumours (2000) Lancet, 355, pp. 716-719. , https://doi.org/10.1016/S0140-6736(99)10238-1
  • Horwitz, G.A., Miklovsky, I., Heaney, A.P., Ren, S.G., Melmed, S., Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression (2003) Molecular Endocrinology, 17, pp. 600-609. , https://doi.org/10.1210/me.2001-0006
  • Huang, C.C., Tu, S.H., Lien, H.H., Jeng, J.Y., Huang, C.S., Huang, C.J., Lai, L.C., Chuang, E.Y., Concurrent gene signatures for han Chinese breast cancers (2013) PLoS ONE, 8, p. e76421. , https://doi.org/10.1371/journal.pone.0076421
  • Huang, S., Liu, Q., Liao, Q., Wu, Q., Sun, B., Yang, Z., Hu, X., Li, L., IL-6/STAT3 promotes prostate cancer resistance to androgen deprivation therapy via regulating PTTG1 expression (2018) Cancer Science, 109, pp. 678-687. , https://doi.org/10.1111/cas.13493
  • Ito, T., Shimada, Y., Kan, T., David, S., Cheng, Y., Mori, Y., Agarwal, R., Olaru, A., Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma (2008) Cancer Research, 68, pp. 3214-3224. , https://doi.org/10.1158/0008-5472.CAN-07-3043
  • Lewy, G.D., Sharma, N., Seed, R.I., Smith, V.E., Boelaert, K., McCabe, C.J., The pituitary tumor transforming gene in thyroid cancer (2012) Journal of Endocrinological Investigation, 35, pp. 425-433
  • Liu, J., Wang, Y., He, H., Jin, W., Zheng, R., Overexpression of the pituitary tumor transforming gene upregulates metastasis in malignant neoplasms of the human salivary glands (2015) Experimental and Therapeutic Medicine, 10, pp. 763-768. , https://doi.org/10.3892/etm.2015.2566
  • Mastronardi, L., Guiducci, A., Buttaro, F.M., Cristallini, E.G., Puzzilli, F., Maira, G., Relationships among DNA index, S-phase, and invasive behavior in anterior pituitary adenomas. A cytometric study of 61 cases with Feulgen-positive DNA analysis (2001) Surgical Neurology, 56, pp. 27-32. , https://doi.org/10.1016/S0090-3019(01)00455-4
  • McCabe, C.J., Gittoes, N.J., PTTG - A new pituitary tumour transforming gene (1999) Journal of Endocrinology, 162, pp. 163-166. , https://doi.org/10.1677/joe.0.1620163
  • Melmed, S., Pathogenesis of pituitary tumors (2011) Nature Reviews Endocrinology, 7, pp. 257-266. , https://doi.org/10.1038/nrendo.2011.40
  • Musat, M., Vax, V.V., Borboli, N., Gueorguiev, M., Bonner, S., Korbonits, M., Grossman, A.B., Cell cycle dysregulation in pituitary oncogenesis (2004) Frontiers of Hormone Research, 32, pp. 34-62
  • Ogbagabriel, S., Fernando, M., Waldman, F.M., Bose, S., Heaney, A.P., Securin is overexpressed in breast cancer (2005) Modern Pathology, 18, pp. 985-990. , https://doi.org/10.1038/modpathol.3800382
  • Paez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grubler, Y., Chervin, A., Hentges, S.T., Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk (2003) PNAS, 100, pp. 1034-1039. , https://doi.org/10.1073/pnas.0237312100
  • Panguluri, S.K., Yeakel, C., Kakar, S.S., PTTG: An important target gene for ovarian cancer therapy (2008) Journal of Ovarian Research, 1, p. 6. , https://doi.org/10.1186/1757-2215-1-6
  • Pei, L., Genomic organization and identification of an enhancer element containing binding sites for multiple proteins in rat pituitary tumor-transforming gene (1998) Journal of Biological Chemistry, 273, pp. 5219-5225. , https://doi.org/10.1074/jbc.273.9.5219
  • Pei, L., Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells (1999) Journal of Biological Chemistry, 274, pp. 3151-3158. , https://doi.org/10.1074/jbc.274.5.3151
  • Pei, L., Melmed, S., Isolation and characterization of a pituitary tumor-transforming gene (PTTG) (1997) Molecular Endocrinology, 11, pp. 433-441. , https://doi.org/10.1210/mend.11.4.9911
  • Perez-Castro, C., Renner, U., Haedo, M.R., Stalla, G.K., Arzt, E., Cellular and molecular specificity of pituitary gland physiology (2012) Physiological Reviews, 92, pp. 1-38. , https://doi.org/10.1152/physrev.00003.2011
  • Quereda, V., Malumbres, M., Cell cycle control of pituitary development and disease (2009) Journal of Molecular Endocrinology, 42, pp. 75-86. , https://doi.org/10.1677/JME-08-0146
  • Ramos-Morales, F., Dominguez, A., Romero, F., Luna, R., Multon, M.C., Pintor-Toro, J.A., Tortolero, M., Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product (2000) Oncogene, 19, pp. 403-409. , https://doi.org/10.1038/sj.onc.1203320
  • Read, M.L., Fong, J.C., Modasia, B., Fletcher, A., Imruetaicharoenchoke, W., Thompson, R.J., Nieto, H., Mallick, U., Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer (2017) Oncogene, 36, pp. 5296-5308. , https://doi.org/10.1038/onc.2017.154
  • Romero, F., Multon, M.C., Ramos-Morales, F., Dominguez, A., Bernal, J.A., Pintor-Toro, J.A., Tortolero, M., Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase (2001) Nucleic Acids Research, 29, pp. 1300-1307. , https://doi.org/10.1093/nar/29.6.1300
  • Saez, C., Japon, M.A., Ramos-Morales, F., Romero, F., Segura, D.I., Tortolero, M., Pintor-Toro, J.A., Hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias (1999) Oncogene, 18, pp. 5473-5476. , https://doi.org/10.1038/sj.onc.1202914
  • Salehi, F., Scheithauer, B.W., Sharma, S., Kovacs, K., Lloyd, R.V., Cusimano, M.D., Munoz, D.G., Immunohistochemical expression of PTTG in brain tumors (2013) Anticancer Research, 33, pp. 119-122
  • Sapochnik, M., Haedo, M.R., Fuertes, M., Ajler, P., Carrizo, G., Cervio, A., Sevlever, G., Arzt, E., Autocrine IL-6 mediates pituitary tumor senescence (2017) Oncotarget, 8, pp. 4690-4702
  • Schneider, B.P., Li, L., Radovich, M., Shen, F., Miller, K.D., Flockhart, D.A., Jiang, G., Vatta, M., Genome-wide association studies for taxane-induced peripheral neuropathy in ECOG-5103 and ECOG-1199 (2015) Clinical Cancer Research, 21, pp. 5082-5091. , https://doi.org/10.1158/1078-0432.CCR-15-0586
  • Shan, B., Gerez, J., Haedo, M., Fuertes, M., Theodoropoulou, M., Buchfelder, M., Losa, M., Renner, U., RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells (2012) Endocrine-Related Cancer, 19, pp. 13-27. , https://doi.org/10.1530/ERC-11-0211
  • Smith, V.E., Franklyn, J.A., McCabe, C.J., Pituitary tumor-transforming gene and its binding factor in endocrine cancer (2010) Expert Reviews in Molecular Medicine, 12, p. e38. , https://doi.org/10.1017/S1462399410001699
  • Solbach, C., Roller, M., Fellbaum, C., Nicoletti, M., Kaufmann, M., PTTG mRNA expression in primary breast cancer: A prognostic marker for lymph node invasion and tumor recurrence (2004) Breast, 13, pp. 80-81. , https://doi.org/10.1016/j.breast.2003.09.008
  • Tong, Y., Eigler, T., Transcriptional targets for pituitary tumor-transforming gene-1 (2009) Journal of Molecular Endocrinology, 43, pp. 179-185. , https://doi.org/10.1677/JME-08-0176
  • Tong, Y., Tan, Y., Zhou, C., Melmed, S., Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition (2007) Oncogene, 26, pp. 5596-5605. , https://doi.org/10.1038/sj.onc.1210339
  • Tong, Y., Ben-Shlomo, A., Zhou, C., Wawrowsky, K., Melmed, S., Pituitary tumor transforming gene 1 regulates Aurora kinase A activity (2008) Oncogene, 27, pp. 6385-6395. , https://doi.org/10.1038/onc.2008.234
  • Tsai, S.J., Lin, S.J., Cheng, Y.M., Chen, H.M., Wing, L.Y., Expression and functional analysis of pituitary tumor transforming gene-1 (corrected) in uterine leiomyomas (2005) Journal of Clinical Endocrinology and Metabolism, 90, pp. 3715-3723. , https://doi.org/10.1210/jc.2004-2303
  • Uccella, S., Tibiletti, M.G., Bernasconi, B., Finzi, G., Oldrini, R., Capella, C., Aneuploidy, centrosome alteration and securin overexpression as features of pituitary somatotroph and lactotroph adenomas (2005) Analytical and Quantitative Cytology and Histology, 27, pp. 241-252
  • Wang, Z., Yu, R., Melmed, S., Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division (2001) Molecular Endocrinology, 15, pp. 1870-1879. , https://doi.org/10.1210/mend.15.11.0729
  • Wang, Z., Moro, E., Kovacs, K., Yu, R., Melmed, S., Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes (2003) PNAS, 100, pp. 3428-3432. , https://doi.org/10.1073/pnas.0638052100
  • Yu, R., Lu, W., Chen, J., McCabe, C.J., Melmed, S., Overexpressed pituitary tumor-transforming gene causes aneuploidy in live human cells (2003) Endocrinology, 144, pp. 4991-4998. , https://doi.org/10.1210/en.2003-0305
  • Zhang, X., Horwitz, G.A., Heaney, A.P., Nakashima, M., Prezant, T.R., Bronstein, M.D., Melmed, S., Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas (1999) Journal of Clinical Endocrinology and Metabolism, 84, pp. 761-767. , https://doi.org/10.1210/jcem.84.2.5432
  • Zhang, X., Horwitz, G.A., Prezant, T.R., Valentini, A., Nakashima, M., Bronstein, M.D., Melmed, S., Structure, expression, and function of human pituitary tumor-transforming gene (PTTG) (1999) Molecular Endocrinology, 13, pp. 156-166. , https://doi.org/10.1210/mend.13.1.0225
  • Zhang, J., Yang, Y., Chen, L., Zheng, D., Ma, J., Overexpression of pituitary tumor transforming gene (PTTG) is associated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma (2014) Acta Histochemica, 116, pp. 435-439. , https://doi.org/10.1016/j.acthis.2013.09.011
  • Zhou, C., Tong, Y., Wawrowsky, K., Melmed, S., PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility (2014) Oncogene, 33, pp. 851-861. , https://doi.org/10.1038/onc.2013.16
  • Zhu, X., Mao, Z., Na, Y., Guo, Y., Wang, X., Xin, D., Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer (2006) Anticancer Research, 26, pp. 1253-1259
  • Zou, H., McGarry, T.J., Bernal, T., Kirschner, M.W., Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis (1999) Science, 285, pp. 418-422. , https://doi.org/10.1126/science.285.5426.418

Citas:

---------- APA ----------
Fuertes, M., Sapochnik, M., Tedesco, L., Senin, S., Attorresi, A., Ajler, P., Carrizo, G.,..., Arzt, E. (2018) . Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity. Endocrine-Related Cancer, 25(6), 665-676.
http://dx.doi.org/10.1530/ERC-18-0028
---------- CHICAGO ----------
Fuertes, M., Sapochnik, M., Tedesco, L., Senin, S., Attorresi, A., Ajler, P., et al. "Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity" . Endocrine-Related Cancer 25, no. 6 (2018) : 665-676.
http://dx.doi.org/10.1530/ERC-18-0028
---------- MLA ----------
Fuertes, M., Sapochnik, M., Tedesco, L., Senin, S., Attorresi, A., Ajler, P., et al. "Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity" . Endocrine-Related Cancer, vol. 25, no. 6, 2018, pp. 665-676.
http://dx.doi.org/10.1530/ERC-18-0028
---------- VANCOUVER ----------
Fuertes, M., Sapochnik, M., Tedesco, L., Senin, S., Attorresi, A., Ajler, P., et al. Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity. Endocr.-Relat. Cancer. 2018;25(6):665-676.
http://dx.doi.org/10.1530/ERC-18-0028