Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype

作者: E C Maggi , J Trillo-Tinoco , A P Struckhoff , J Vijayaraghavan , L Del Valle

DOI: 10.1038/ONCSIS.2016.58

关键词:

摘要: Neuroendocrine tumors (NETs), which can have survival rates as low 4%, currently limited therapeutic interventions available highlighting the dire need for identification of novel biological targets use new potential drug targets. One such target is retinoblastoma-binding protein 2 (RBP2), an H3K4 demethylase whose overexpression has been linked to cancer formation and metastasis in non-endocrine tumor types. We measured RBP2 mRNA levels enteropancreatic NETs by measuring matched human normal NET tissue samples. Further, proliferation, migration, invasion colony assays were performed physiologically relevant cell lines βlox5, H727 QGP-1 understand role its activity on end points tumorigenesis. Our data indicate a strong correlation between expression specimens. was overexpressed relative tissue-matched controls 80% measured. In vitro studies showed significantly increased formation, whereas knockdown decreases same parameters demethylase-independent manner. The cycle inhibitors p21 p57 decreased with upon depletion, suggesting regulatory cellular proliferation. Taken together, our results support hypothesis that aberrant frequent contributing factor NETs.

参考文章(33)
Dimitrios Karakaxas, Maria Gazouli, Theodoros Liakakos, Anna Vaiopoulou, Dimitra Apessou, Kleo Papaparaskeva, Pavlos Patapis, Christos Dervenis, Pancreatic neuroendocrine tumors: current opinions on a rare, but potentially curable neoplasm European Journal of Gastroenterology & Hepatology. ,vol. 26, pp. 826- 835 ,(2014) , 10.1097/MEG.0000000000000138
E Mitry, E Baudin, M Ducreux, J-C Sabourin, P Rufié, T Aparicio, P Lasser, D Elias, P Duvillard, M Schlumberger, P Rougier, Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin British Journal of Cancer. ,vol. 81, pp. 1351- 1355 ,(1999) , 10.1038/SJ.BJC.6690325
Edel Kavanagh, Bertrand Joseph, The hallmarks of CDKN1C (p57, KIP2) in cancer. Biochimica et Biophysica Acta. ,vol. 1816, pp. 50- 56 ,(2011) , 10.1016/J.BBCAN.2011.03.002
Wenshu Ge, Lei Shi, Yongsheng Zhou, Yunsong Liu, Gui-e Ma, Yong Jiang, Yongwei Xu, Xiao Zhang, Hailan Feng, Inhibition of osteogenic differentiation of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription. Stem Cells. ,vol. 29, pp. 1112- 1125 ,(2011) , 10.1002/STEM.663
T Takahashi, M. Nau, I Chiba, M. Birrer, R. Rosenberg, M Vinocour, M Levitt, H Pass, A. Gazdar, J. Minna, p53: a frequent target for genetic abnormalities in lung cancer Science. ,vol. 246, pp. 491- 494 ,(1989) , 10.1126/SCIENCE.2554494
W. Lin, J. Cao, J. Liu, M. L. Beshiri, Y. Fujiwara, J. Francis, A. D. Cherniack, C. Geisen, L. P. Blair, M. R. Zou, X. Shen, D. Kawamori, Z. Liu, C. Grisanzio, H. Watanabe, Y. A. Minamishima, Q. Zhang, R. N. Kulkarni, S. Signoretti, S. J. Rodig, R. T. Bronson, S. H. Orkin, D. P. Tuck, E. V. Benevolenskaya, M. Meyerson, W. G. Kaelin, Q. Yan, Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1 Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 13379- 13386 ,(2011) , 10.1073/PNAS.1110104108
Xiuming Liang, Jiping Zeng, Lixiang Wang, Ming Fang, Qing Wang, Min Zhao, Xia Xu, Zhifang Liu, Wenjuan Li, Shili Liu, Han Yu, Jihui Jia, Chunyan Chen, Histone Demethylase Retinoblastoma Binding Protein 2 is Overexpressed in Hepatocellular Carcinoma and Negatively Regulated by hsa-miR-212 PLoS ONE. ,vol. 8, pp. e69784- ,(2013) , 10.1371/JOURNAL.PONE.0069784
Gabriel M. Gutierrez, Elizabeth Kong, Philip W. Hinds, Master or slave: The complex relationship of RBP2 and pRb Cancer Cell. ,vol. 7, pp. 501- 502 ,(2005) , 10.1016/J.CCR.2005.05.021
Chris van Oevelen, Jinhua Wang, Patrik Asp, Qin Yan, William G. Kaelin, Yuval Kluger, Brian David Dynlacht, A role for mammalian Sin3 in permanent gene silencing Molecular Cell. ,vol. 32, pp. 359- 370 ,(2008) , 10.1016/J.MOLCEL.2008.10.015
Dorian R.A. Swarts, Frans C.S. Ramaekers, Ernst-Jan M. Speel, Molecular and cellular biology of neuroendocrine lung tumors: Evidence for separate biological entities Biochimica et Biophysica Acta. ,vol. 1826, pp. 255- 271 ,(2012) , 10.1016/J.BBCAN.2012.05.001